Paper - Comparative studies on the growth of the cerebral cortex 7 (1918)
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Sugita N. Comparative studies on the growth of the cerebral cortex. VII. On the influence of starvation at an early age upon the development of the cerebral cortex. Albino rat. (1918) J Comp. Neurol. 29: 177-.
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Sugita N. Comparative studies on the growth of the cerebral cortex. II. On the increases in the thickness of the cerebral cortex during the postnatal growth of the brain. Albino rat. (1917) J Comp. Neurol. 28: 511-. Sugita N. Comparative studies on the growth of the cerebral cortex. III. On the size and shape of the cerebrum in the Norway rat (Mus norvegicus) and a comparison of these with the corresponding characters in the albino rat. (1918) J Comp. Neurol. 29: 1-. Sugita N. Comparative studies on the growth of the cerebral cortex. IV. On the thickness of the cerebral cortex of the Norway rat (Mus norvegicus) and a comparison of the same with the cortical thickness in the albino rat. (1918) J Comp. Neurol. 29: 11-. Sugita N. Comparative studies on the growth of the cerebral cortex. V. Part I. On the area of the cortex and on the number of cells in a unit volume, measured on the frontal and sagittal sections of the albino rat brain, together with the changes in these characters according to the growth of the brain. V. Part II. On the area of the cortex and on the number of cells in a unit volume, measured on the frontal and sagittal sections of the brain of the Norway rat (Mus norvegicus), compared with the c responding data for the albino rat. (1918) J Comp. Neurol. 29: 61-117. Sugita N. Comparative studies on the growth of the cerebral cortex. VI. Part I. On the increase in size and on the developmental changes of some nerve cells in the cerebral cortex of the albino rat during the growth of the brain. VI. Part II. On the increase in size of some nerve cells in the cerebral cortex of the Norway rat (Mus norvegicus), compared with the corresponding changes in the albino rat. (1918) J Comp. Neurol. 29: 119-. Sugita N. Comparative studies on the growth of the cerebral cortex. VII. On the influence of starvation at an early age upon the development of the cerebral cortex. Albino rat. (1918) J Comp. Neurol. 29: 177-. Sugita N. Comparative studies on the growth of the cerebral cortex. VIII. General review of data for the thickness of the cerebral cortex and the size of the cortical cells in several mammals, together with some postnatal growth changes in these structures. (1918) J Comp. Neurol. 29: 241-.
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Comparative Studies on the Growth of the Cerebral Cortex
VII. On the Influence of Starvation at an Early Age upon the Development of the Cerebral Cortex. Albino Rat
From The Wistar Institute of Anatomy and Biology
Two Charts
- This study was carried on from October, 1916 to July, 1917, at The Wistar Institute of Anatomy and Biology.
1. Introduction
Investigations on the influence of partial or complete starvation upon the growth of the body under various conditions have been made by many authors, and it has long been known that of all the organs the brain is least affected in weight by underfeeding while, in younger animals in active growth, the brain weight may even increase during severe underfeeding. These facts were early observed by Chossat ('43) in pigeons, Falck ('54) in dogs and Voit ('66) in cats, later by Bechterew ('95) in kittens and puppies and Lassarew ('97) in guinea-pigs, and recently by Hatai ('04, '08, '15), Donaldson ('11), Jackson ('15 a, '15 b), and others working in the albino rat. Jackson made experiments with complete and partial starvation on adult albino rats and also held the young albino rats at constant body weight for a considerable period by partial underfeeding, and in all his experiments the brain was found to be only slightly affected in weight. Hatai underfed young rats so as to cause a reduction of 30 per cent in total body weight, while the average loss in brain weight was only 5 per cent. According to Donaldson's experiments on the young albino rats (thirty days old) under moderate underfeeding for three weeks, it was found that the underfed are on the average 41.2 per cent less in body weight than the controls and nevertheless only 7.7 per cent less in brain weight.
According to lYiy previous studies on the normal development of the cerebral cortex during the period of most active growth (Sugita, '17, '17 a, '18 a, '18 b, '18 c), it was found that the growth of the cortex is precocious and that its elementary organization (that is, the cortical thickness, the cortical cell number and cell size, etc.) is nearly completed at the time of weaning, when the albino rat is twenty days of age. The investigations by the several authors cited above were, however, made mostly on animals which were already weaned, because, of course, feeding experiments necessitate a strict food control. But at this stage (after weaning), the elementary organization of the cerebral cortex is already completed. For my object, which was to determine the effect of starvation on the early development of the cerebral cortex, it was necessary to use animals in which the growth of the cerebral cortex was still in active progress and to note the influence upon the organization of the cortex of longer and shorter periods of inadequate feeding.
For this it is necessary to use the very young animals, still dependent on the mother. During this period the growth impulse in the brain is especially strong and the results of underfeeding are somewhat peculiar, as the brain weight may even increase under severe underfeeding. In complete starvation, growth is stopped and the brain weight remains constant. Thus, von Bechterew ('95) studied on new-born kittens and puppies the influence of complete starvation upon the brain w^eight. His results were that the brain weight, at the time of death after three or four days of starvation, was like the initial weight of the organ at birth. The brain had not grown, but also it had not lost in weight.
By applying severe starvation to the albino rat immediately after birth, it has been my object in the present study to obtain answers to the following questions:
- How far will the growth of the body and of the brain be arrested?
- Will the normal relation between body weight, body length, and tail length be modified?
- What will be the relation between body weight and brain weight in the underfed rats?
- How far will the size and shape of the cerebrum be influenced?
- Will the thickness of the cortex of the stunted rats be different from that of the standard?
- How far will the Volume of the cerebral cortex be modified?
- Will the number of the cortical cells increase normally according to age?
- Will the development in the size of the nerve cells be influenced by starvation?
- What will be the effect of the starvation on the percentage of water and on the alcohol extractives?
2. The Test Animals
After several preliminary tests on producing underfed young, I adopted the following three procedures, which are fairly reliable:
I. Separation of the young from the nursing mother for a maximum period each day.
II. Entrusting one mother with an excessive number of young and thus reducing the amount of milk available for each of the young.
III. Underfeeding the nursing mother and thus reducing the quantity of milk secreted.
I treated five litters by the first method (Series I), two litters by the second method (Series II), and one litter by the third method (Series III). The detailed records of these experiments are on file at The Wistar Institute of Anatomy and Biology. All the material, consisting of forty-six test individuals and fourteen controls, from the above eight litters, was supplied from the rat colony at The Wistar Institute. They are all from mothers of standard size which were kept throughout the experiment under good sanitary conditions.
3. Material
Series I (Litters A, B, C, D, and E, table 1)
Procedure. In each litter, half of the young were selected for the experiment and marked with hectograph ink on the back and the remaining individuals were used as the controls. The young under experiment were taken away from 'the mother each day and kept packed in cotton in a warm place, but without any food or water, for the time which had been determined. Table 1 contains the records of the number of hours during which each test individual in this series was isolated each day.
Litter A {horn October 16, 1916) was composed of nine young. Five (c, a, d, f, and h) were subjected to experiment and were separated from the mother daily beginning on the very day of birth, the f oodless interval being increased day by day, as recorded in table 1. Sundays were excluded from any experimentation. The duration of starvation, daily and total, and the age at which the animals were killed is recorded also in table 1. Four controls (b, e, g, and i) were also killed one by one at the same' ages as the test animals. The total hours of isolation, the average per day, and the percentage of hours isolated during the total life of the individual in hours, are given in the lower part of the table. As the young are not fed continuously, even when they were with the mother, this percentage will but roughly indicate the grade of underfeeding to which the young were subjected. They were killed for examination at the ages of 3, 4, 9, 11, and 15 days (see X in table 1).
Litter B {born October 15, 1916) consisted of ten young. Five (a, c, e, f and i) were separated daily from their mother, as in the case of Litter A, and the remaining young (b, d, g, h, and j) were used as controls. The experiment was begun at the age of one day in Litter B, a day later than in the case of Litter A. They were killed for examination at the ages of 4, 8, 11, 12, and 19 days.
Litter A and B represent groups in which mild starvation was instituted from a very early age.
Litter C {born October 18, 1916) was composed of seven young, of which four (a, c, d, and f) were used for experiment and three (b, e, and g) for control. The experiment was begun five days after birth. One test rat (f) and one control (g) were killed by the mother. For the first three days mild starvation was tried, and then, from the age of nine days, severe starvation was instituted. They were killed for examination at the ages of '15, 17, and 28 days.
Litter D {horn October 23, 1916) consisted initially of eight young, of which five (a, c, d, e, and g) were used for experiment and three (b, f, and h) for control. One underfed (g) and one control (h) were killed by the mother. In this litter severe starvation was begun at the age of three days. The animals were killed at the ages of 9, 10, 16, and 18 days.
Litter E {horn Novernher 4, 1916\ was composed of eight rats, of which six (a, b, c, d, g, and h) were selected for experiment and two (e and f) for control. Severe starvation with some intervals of feeding was begun at the age of three days. In this litter pairs of test rats of the same age were killed for examination (on the 7th, 10th, and 17th days of the experiment) to determine individual variations.
Litters D and E represent groups in which relatively severe starvation was begun at an early age.
Series II {Litters F and H)
Procedure. In this series one nursing mother was placed in charge of an excessive number of young. The results were not very good, because some relatively lucky or strong ones always got more than their share of milk, while the others were in a condition of severe underfeeding.
Litter F {horn Octoher 15, 1916). To a young small primipara, which had just given birth to ten young, were entrusted ten more young from two other litters which had been born on the same day. Unhappily, the young from three different litters were not separately marked. The rate of growth among them was later found to be unequal, owing probably partly to litter characteristics and partly to the inequality of the milk ration. Individuals were selected arbitrarily and killed for examination at intervals of one to three days (at the ages of 11, 14, 17, 19, 20, 23, 24, 26, 30, and 40 days). Those killed were replaced by individuals of like age from other litters, so as to keep the number in this litter always above thirteen. After twenty days, the mother was removed and the young fed with a small amount of ordinary food. The last eight young, which survived beyond the age of forty days, were rejected as too old for the purpose of this study.
Litter H {born January 2, 1917). A mother having just given birth to eight young was entrusted with nine more young from another litter which had been born on the same day. The underfed young of this litter were all employed for the study on the percentage of water and for the histological study of myelination in the brain and not included in the study of the cerebral cortex.
Series III {Litter G)
Litter G (born October 23, 1916). In this series a nursing mother was severely underfed immediately after the parturition. This litter consisted of eleven young. Only a fraction (one-tenth to one-twentieth) of the ordinary diet with unlimited water was supplied daily to the mother. She was found to lose slowly in body weight day by day. The amount of milk was consequently much reduced, but not completely stopped, as could be determined by examining daily the stomach contents of the young. By this method I was able to get a series of young which were very poorly developed. The young were killed for examination at the ages of 8, 10, 11, 12, 15, 16, 18, 22, and 25 days.
Table 2 contains the observed body weight and brain weight of the young in Litters F, G, and H, when examined, for a comparison with table 1.
4. Body Weight, Body Length and Tail Length
Table 3a (not published, because of its complexity, but on file at The Wistar Institute), gives for each individual in this study the sex, age, observed body length, tail length, and brain weight. The standard tail length and the standard brain weight for the observed body length were also entered for comparison, the
TABLE 2
Showing for each test individual in Series II and III (Litters F, G, and H) the sex, age, and body and brain loeights, at time of examination
LITTER (series II AND III)
SEX
AGE OF KILLING
BODY WEIGHT
BRAIN WEIGHT
days
grams •
grains
Fa
m
11
8.5
0.709
b
f
14
9.8
•0.954
c
f
17
13.5
1.106
d
f
19
13.3
1.218 •
e
m
20
12.4
1.148
f
m
23
11.2
1.230
g
f
• 23
14.2
1.224
h
m
24
13.5
1.170
i
f
26
17.0
1.197
J
f
30
24.2
1.219
k
m
30
18.7
1.222
1
f
40
40.0
1.310
Ga
m
8
7.5
0.679
b
f
8
7.4
0.703
c
f
10
10.3
0.864
d
m
11
9.8
0.929
e
f
12
8.8
0.907
f
m
15
7.3
0.881
g
in
16
7.3
0.948
h
m
18
9.6
1.119
i
f
22
12.2
1.110
J
m
25
17.2
1.234
Ha
f
13
8.8
0.880
b
f
17
10.8
1.024
c
f
23
14.7
1.135
d •
f
28
17.2
1.166
e
m
32
20.0
1.215
f
f
37
19.3
1.101
g
m
43
21.1
1.295
values having been calculated for each individual by the use of formulas given in 'The Rat' (Donaldson, '15). Here the body length was chosen as the basis for comparison, because the increase in body length has proved less variable than body weight. Table 3 was condensed from the original complete table (table 3a) by dividing the individuals, the tests, and controls within each litter into two groups, according to the observed brain
186 NAOKI SUGITA
weight and taking averages for each group. Group I consists of those which have brains weighing less than 1.0 gram and presumably still in the first phases of cortical development (Sugita, '17 a) and Group II those which have brains weighing more than 1.0 gram and probably in the second or third phase of cortical development. So, one litter in Series I was divided into four groups, the tests having brain weights less than 1.0 gram (T. I), the tests having brain weights more than 1.0 gram (T. II), the controls having brain weights less than 1.0 gram (C. I) and the controls having brain weights more than 1.0 gram (C. II). This grouping prevails throughout all condensed tables (tables 3 to 13, 16 and 17) published in this paper. The average values were all obtained according to individual measurements, and the average standard values were also obtained by averaging from the full tables, which give the individual cases. As the standard values were not based on the average measurements given in the condensed tables, those standards given in the condensed tables sometimes deviate slightly from the standard values which would be directly obtained for the given average measurements.
On comparing, in table 3, the observed measurements with the corresponding standards, no significant difference between them has been detected, either in the underfed or in the controls. Only the body weight in the underfed is slightly lower as compared with the standard for the same body length, but it amounts to no more than 8 per cent.
This comparison indicates that, though the underfed young show a considerable retardation in total growth according to age (see table 4), yet the relation between the body and the tail lengths and the body weight is but little affected, at least during the early period of active growth. So the only marked difference between the underfed and the controls of the same body length or body weight would be the age, if their brain weights are disregarded. The effect on the brain weight will be discussed in the next chapter.
GROWTH OF THE CEREBRAL CORTEX
187
TABLE 3
Giving for each litter group in this sttidy the average age, body length, tail length, and body weight, the last two compared with the corresponding standard measurements for the observed body length, calculated according to sex by the use of formulas given in 'The Rat' 'Donaldson, '15). The general averages for the test and the control groups are given at the foot of the table. T = test, C = control.
TEST CONTROL
SEX
AVERAGE AGE
BODY
LENGTH
TAIL LENGTH
BODY WEIGHT
SERIES, LITTER AND GROUP
Observed
standard
aocord ina to
body
length
Observed
Standard according to bodylength
Series 1
A c, a, d, f
h
b, e, g i
T. I T. II
C. I C. II
1 m, 3 f 1 f
3 m 1 f
days
715
8 17
ni m .
56.3 74.0
66.7 96.0
mm.
26.5 48.0
31.7 62.0
mm. 26.3 47 .0
37.0
71.0
grams
7.2
13.9
11.7 30.1
grams 7.1
13.9
10.2 26.3
Series I
B a, c, e, f
i
b, d g, h, j
T. I T. II
C. I C. II
3 m, 1 f 1 m
2f 3f
919
6
18
59.8 75.0
57.0 86.3
27.8 50.0
25.5 53.3
29.8 46.0
27.5 61 3
7.3 12.7
7.1 20.5
7.9 13.6
7.0 20.3
Series I C a, c, d
b, e
T. II C. II
2 m, 1 f 2 f
20 22 —
82.0 98.5
51.7 71.5
54.3 73.5
15.1
27.6
17.5 29.4
Series I
D a, c, d
e
b
f
T. I T. II
C. I C. II
1 m, 2 f 1 m
1 m 1 m
12 18
9 22
61.0
78.0
69.0 91.0
39.0 54.0
39.0 65.0
31.7 49.0
40.0 63.0
6.9 13.0
11.2 24.0
8.2 15.0
1.0
21.9
Series I
E a, b, c, d
g, h
e, f
T. I T. II
C. II
3 m, 1 f 2 f
1 m, 1 f
1220
17
65.8 82.0
87.0
35.0 58.0
56.5
36.8 56.0
60.0
9.7 16.2
21.6
9.9 17.9
0.4
Series II
Fa, b
c-1
T. I T. II
1 m, I'f 4 m, 6 f
13 25+
63.5 83.9
33.0 61.5
34.5 57.1
9.2 18.1
9.1 19.4
TABLE Z — Continued
TEST CONTROL
SEX
AVE RAGE AGE
BODY LENGTH
TAIL LENGTH
BODY WEIGHT
SERIES, LITTER AND GROUP
Ob
Standard accord
Ob
Stsadard accord
served
ing to body length
served
ing to body length
days
mm.
7)1 m.
mm.
grams
grams
Series III
Ga-g
T.
I
4 m, 3 f
11 +
63.0
32.9
33.7
8.3
8.8
h-j
T.
II
2m, If
22
7i.O
48.7
46.7
13.0
14.1
Series II
H a
T.
I
1 f
13
63.0
33.0
34.7
8.8
9.
b-g
T.
II
2 m, 4 f
30
81.7
64.0
53.8
17.2
17.1
Average 1
T.
I
11
61.8
32.5
32.5
8.2
8.6
.(Series I-III)J
T.
II
21+
79.0
54.5
51.2
14.9
16.1
Average )
C.
I
8
64.2
32.1
34.8
10.0
9.4
(Series I)/
C.
II
19+
91.8
61.7
65.8
24.8
23.7
5. Body Weight And Brain Weight
Table 4 was condensed from table 4 a (unpublished), which gives data for each individual in this study, and shows for each group, in the three series, the sexes, average age, average duration of starvation (denoted by percentage value of the hours of isolation), and the observed body and brain weights, accompanied by the average values for the group of the individual standard weights, for the same ages, and of the individual standard brain weights for the same ages and for the same body weights. For the calculation of the standard values for each individual the sex was regarded, because in body and brain weights the sex difference is clear ('The Rat,' Donaldson, '15). The average differences of the observed values from the standards are given for each group in percentage, the standards being taken, respectively, as the norms for comparison.
A glance at the table reveals three differences which are clearly marked :
- The underfed rats have, as a rule, body weights considerably less than the standard values for the same age.
- The underfed rats have brain weights somewhat less than the standard values for the same age.
- The underfed rats have brain weights mar" edly higher than the standard values for their observed body weight.
It was already noted in the introduction that the central nervous system as represented by the brain suffers little or no loss of initial weight even in the case of severe starvation. In my series-T-underfeeding of the albino rat at an early age — the body weight of the rats stunted by starvation, as compared with the standards for the same age, were deficient (on the average by litters, table 4) by from 19 to 44 per cent. On the other hand, the brain weights were less than the standards for the same age by from 4 to 12 per cent (for litters, table 4, but by from 3 to 17 per cent for individuals, table 4 a), while for the same body weights they were from 15 to 29 per cent (for litters, table 4, but up to 65 per cent for individuals, table 4 a) above the standard values.
Considering together all the five litters (A to E) of Series I, in which the young were starved by separating them at an early age from the mother daily, it appears that the underfed rats at the end of the first twenty days after birth (during the suckling period) are about 29 per cent (average of A, T. I and II, B, T. I and II, C, T. II, D, T. I and II, and E, T. I and II) behind the standards in body weight, while they are only 8 per cent (averge of the above-cited cases) behind in the brain weight. In Series II and III, in both of which the young were subjected to early and continuous underfeeding, increasing in intensity, by the method of reducing the ration of milk, but without removal from the nest, the underfed young have shown a slightly better development in brain weight (in relation to body weight), the average being also 8 per cent (average of F, T. I and II, G, T. I and II, and H, T. I and II) less than the standard for the same age, while the body weight is on the average as much as 39 per cent (average of the above-cited cases) below the standard value. Whether removing the young from the nest increases the relative effect of underfeeding on the brain, as these results suggest, can be determined only by experiments with that question as the main point in view.
In connection with the underfeeding, as practiced in Series I, some interesting results of overfeeding have been noticed in the control animals ; overfeeding having taken place in the case of the controls of Litters A to E on account of the periodic isolation of a number of the members of the litter. The controls have shown generally, as seen in table 4 a (unpublished) and also in table 4, some excess in body and brain weights, as compared with the standard values for the same age. The excess in body weight is on the average 19 per cent (average of A, C. I and II, B, C. I and II, C, C. II, D, C. I and II, and E, C. II), while the brain weight is on the average 6 per cent (average of the above-cited cases) higher than the standard for the same age and 2 per cent higher than the standard for the same body weight. Thus, by moderate overfeeding, the growth in body weight is definitely accelerated and, at the same time, the growth in brain weight is also accelerated, nearly in proportion to the increase in body weight.
If the observed brain weights are compared with the standard brain weights for the observed body weight, it is clearly seen that the observed brain weights are higher than the standard by 24 per cent (average of all eight litters T. groups only). Of course, the younger the individual, the higher is the percentage, because the standard brain weight is smaller in the young animals and they are not increasing in direct proportion to the body weight, but nearly as the logarithm of the latter value. So it may be roughly stated that the brain weights in the underfed young albino rats have values below the standard weights for the same age and above those for the same body weights, but always falling nearer to the standard age values.
6. The Size and Shape of the Cerebrum
The five diameters of the cerebrum of the underfed young were measured and recorded according to the procedure already described in my first paper of this series (Sugita, '17, figs. 1 and 2). The measurement W.B, represents the greatest frontal diameter; the measurement W.D, the frontal diameter passing the middle point of the fissura sagittalis; the measurement L.G, the greatest distance from the frontal pole to the occipital
TABLE 4 Showing for each litter group in this study the average age, duration of isolation denoted by the percentage of the life span, observed body weight, compared with the standard body weight for the same age, and observed rain weight, compared with the standard values for the same age and the observed body weight, respectively. Standard values were all calculated by the use of the formulas given in 'The Rat' (Donaldson, '15). Within each litter the starved animals were divided nto two groups, T I having brains weighing less than 1.0 gram and T. II having brains weighing more than 1.0 gram. The control animals were also grouped in the same way into two groups, C. I and C. II. Averages ivere taken within each group. In lines designated 'percentage difference' (abbreviated 'per. diff.'), the deviations of the observed measuremmts from the standard values were given in percentage, the respective standard values being taken as standards of comparison. At the foot of the table, the average as to the test and control groups are given and the percentage differences from the standards are also caculated
TEST CONTROL
SEX
AVERAGE AGE
a a w
d fc
K « Eh 1
BODY WEIGHT
BRAIN WEIGHT
SERIES, LITTER AND GROUP
Observed
Standard according to age
Ob served
Stanflard according to age
Standard according to observed body weight
days
per cent
gramf
(jrains
grams
grams
grams
Series I
A 0, a, d, f
T. I
1 m, 3 f
t —
32
7.2
.9.7
0.584
0.6U
0.441
h
T. II
1 f
15
44
13.9
16.5
1.C24
1.048
0.952
(per. diff.)
(-19)
(- 5)
(+15)
b, e, g
C. I
3 m
S
11.7
10.9
0.740
0.750
0.790
i
C. II
1 f
17
30.1
18.1
1.278
1.099
1.301
(per. diff.)
(+44)
(+ 9)
(- 4)
Series I
B a, c, e, f
T. I
3 m, 1 f
9
30
7.3
in
0.644
0.775
0.468
i
T. II
1 m
19
44
12.7
18.7
1.052
1 .131
0.901
(per. diff.)
(-34)
(-11)
(+24)
b, d
C. I
2 f
6
7.1
8.6
0.543
0.559
0.437
g. h, J
C. II
3 f
18
20.5
18.7
1.144
1.112
1.148
(per. diff.)
(+ 1)
(+ 1)
(+ 6)
Series I
C a, c, d
T. II
2 in, 1 f
20
44
15.1
20.4
1.105
1.146
0.946
(per. diff.)
(-26)
(- 4)
(+17)
b, e
C. II
2 f
22
27.6
22.6
1.307
1.165
1.234
(per. diff.)
(+22)
(+12)
+ 6)
192
NAOKI SUGITA
TABLE i— Continued
TEST CONTROL
SEX
AVERAGE AGE
5 H H 3 2; b Q 0. 1=
« 2 > a
K > 6, CO
BODT WEIGHT
BRAIN WEIGHT
SERIES, LITTER AND GROUP
Observed
Standard according to age
Observed
Standard according to age
Standard according to observed body weight
Series I D a, c, d
e (per. diff.)
b
f
(per. diff.)
T. I T. II
C. I C. II
Im, 2f
1 m
1 m 1 m
days
12 18
9 22
per cent
57 65
grams
6.9 13.0
11.2 24.0
grams
14.0
18.0
(-38)
11.8 21.1 (+ 7)
grams
0.778 1.089
0.870 1.220
grams 0.943
1.112 (- 9)
0.840 1.184
(+ 3)
grams . 0.437
0.921
(+37)
0.782 1.237 (+ 4)
Series I E a, b, c, d
(per. diff.)
e. f (per. diff.)
T. I T. II
C. II
3m, If 2f
Im, If
1220
17
46 44
9.7 16.2
21.6
14.3 20.7 (-26)
17.S (+25)
0.835 1.122
1.179
0.977 1.159
(- 8)
1.077 (+ 9)
0.664
1.042
(+15)
1.171 (+ 1)
Series II
Fa, b
c-1
(per. diff.)
T. I T. II
Im, If 4 m, 6 f
13 25+
9.2 18.1
14.9 25.6 (-33)
0.832 1.204
1.000 1.231 (- 9)
0.631 1.046
(+21)
Series III
Ga-g
h-j
(per. diff.)
T. I T. II
4 m, 3 f 2m, If
11+ 22
8.3 13.0
13.6 21.5 (-39)
0.844 1.154
0.914 1.181
(- 5)
0.561 0.871 (+39)
Series II
H a
b-g (per. diff.)
T. I T. II
1 f 2 m, 4 f
13 30
8.8 17.2
15.1 31.5
(-44)
0.880 1.156
1.003 1.298 (-12)
0.600 1.045 (+24)
Average 1
(Series I-III)J
(per. diff.)
Average }
(Series I-III)j
(per. diff.)
T. I T. II
11 21 +
8.2 14.9
13.3 (-38)
21.6 (-31)
0.771 1.113
0.895
(-14)
1 . 163
(- 4)
0.543 (+42)
0.966
(+15)
GROWTH OF THE CEREBRAL CORTEX
193
TABLE i— Continued
TEST CONTROL
SEX
AVERAGE AGE
. !Z H W O O fa
p. K
BODY WEIGHT
BRAIN WEIGHT
SERIES, LITTER AND GROUP
Observed
Standard according to age
Observed
Standar 1 according to age
Standard according to observed boily weight
Average 1
(Series I) J
(per. diff.)
C. I
days
8
per cent
grn7ns
10.0
grams
10.4
(- 4)
grams
0.718
grains 0.716
(+ 0)
grams
0.670
(+7)
Average \
(Series I) /
(per. diff.)
C. II
19+
24.8
19.6
(+27)
1.226
1.127 (+ 9)
1.218
(+ 1)
pole; the measurement L.F, the sagittal diameter from the frontal to the occipital pole running parallel to the sagittal fissure, and the measurement Hi. is the greatest vertical height at the stalk of the hypophysis. In table 5, which was condensed from table 5 a (unpubhshed) for each individual, the average brain weight, the average measurements W.B, L.G and Ht. are given for each group, both test and control, compared with the corresponding standard measurements for the brains of the same weight, which were originally calculated for each individual using the formulas formerly presented by me (Sugita, '17), and then condensed. The measurements L.F and W.D are given, also condensed for each group, in table 9.
On examining table 5, it appears that the measurement W.B of the underfed is smaller on the average by 2 per cent (average of all eight litters, T. groups only) than standard for the brains of the same weight, while the measurement L.G of the underfed is greater on the average by 2 per cent (average of all eight litters, T. groups only). The height in the underfed seems to be slightly less, by about 1 per cent on the average. On the other hand, if the controls be considered in the same way, they show also slight deviations from the calculated standard values, thus, on the average (Litters A to E, C. groups only), W.B is smaller by 1 per cent, L.G greater by 0.8 per cent and Ht. smaller by about 3 percent in the controls. As a matter of fact, the measurement of Ht. could not be so accurate on' account of difficulty in fixing the dorsal limit, so that these slight differences in Ht. should not be taken too seriously. The measurement of L.G and W.G can be made accurately so that these results are trustworthy.
Taking these deviations in the controls into account, the general statement may be made that underfeeding alters the shape of the cerebrum, so that it becomes slightly elongated, when compared with the normal cerebrum of the same weight. This difference is probably due to the fact that, although the underfed cerebrum is arrested in growth, it nevertheless tends to enlarge normally and, as already determined (Sugita, '17) becomes more and more elongated as the age advances.
If, for the brains of like weight, the width-length indices obtained bv the formula are compared between the underfed and the controls (compare table 9) or the standard values (based on table 3, Sugita, '17), it will be seen that the index value tends to be lower in the underfed, especially in the members of Litters F and G which were underfed continuously and rather severely. In the latter litters the index values for each individual are smaller by 2 to 7 points than the index values for the standard brains of like weights (the data for these calculations are contained in table 9 a, not here published). The average index values in Litters F and G are 102 (for T. I groups) and 97 (for T. II groups), while the corresponding standard values are, respectively, 106 and 103 (Sugita, '17).
7. Thickness of the Cerebral Cortex
Tables 6 a, 6 b, and 6 c (all unpublished) were originally prepared to give the cortical thickness for each individual as measured at the localities I to VIII in the sagittal and frontal sections and to give the average cortical thickness in each section and the general average thickness, to be compared with the respective standards presented in a former paper (Sugita, '17a). Table 6, which follows, contains in condensed form the corrected data for the thickness of the cerebral cortex of the underfed Albinos and that of
TABLE 5
Giving for each litter group in this study the average brain weight and the average tneasurements L.G, W.B and Hi. of the cerebrum, each corn-pared with the corresponding standard values for the same brain weight, calculated by the use of the for7nulas given by. me (Sugita, '17). The averages for the test and control groups are given at the foot of the table.
SERIES, LITTER AND
TEST CONTROL
AVERAGE BRAIN WEIGHT
W.
B.
L.
G.
Ht.
Observed
Standard
Observed
Standard
Observed
Standard
grams
turn.
mm.
mm.
Tnm.
mm.
mm.
Series I
A c, a, d, f
T.
0.584
10.79
10.94
9.69
9.20
6.99
7.06
h
T.
1.024
13.05
13.00
12.30
12.30
8.45
8.70
b, e, g
C.
0.740
11.63
11.90
10.73
10.63
7.50
7.68
i
C.
1.278
13.85
14-00
13.15
13.25
8.95
9.30
Series I
B a, c, e, f
T.
0.644
11.11
11.38
10.25
9.96
7.36
7.38
i
T.
1.052
13.20
13.15
12.35
12.40
8.50
8.75
b, d
C.
0.543
10.50
10.78
9.73
9.18
6.90
6.95
g., h, j
C.
1.144
13.47
13.48
12.75
12.77
8.68
9.00
Series I
C a, c, d
T.
1.105
13.10
13.35
12.72
12.62
8.70
8.88
b, e
C.
1.307
13.78
14-10
13.63
13.33
8.83
9.40
Series I
D a, c, d
T.
0.778
11.67
12.17
11.25
10.80
7.98
7.92
e
T.
1.089
12.90
13.30
12.75
12.55
8.60
8.85
b
C.
0.870
12.25
12.60
11.40
11.65
8.00
8.20
f
C.
1.220
13.95
13.80
13.30
13.05
8.80
9.20
Series I
E a, b, c, d
T.
0.835
12.08
12.41
11.35
11.16
8.29
8.10
g, h
T.
1.122
13.35
13.40
12.68
12.70
8.98
8.95
e, f
C.
1.179
13.55
13.60
12.78
12.85
8.88
9.05
Series II
F a, b
T.
0.832
12.00
12.53
11.50
11.13
7.95
8.05
c-1
T.
1.204
13.30
13.73
13.11
12.98
9.30
9.15
Series III
Ga-g •
T.
0.844
12.22
12.46
11.46
11.32
8.13
8.69
h-j
T.
1.154
13.27
13.53
13.03
12.80
8.95
9.00
Average 1
T.
0.753
11.65
11.98
10.92
10.60
7.78
7.87
(Ser. I-III)J
T.
1.107
13.17
13.35
12.71
12.62
8.78
8.90
Average 1
C.
0.718
11.46
11.76
10.62
10.49
7.47
7.61
(Ser. I) /
C.
II.
1.226
13.72
13.80
13.12
13.05
8.83
9.19
195
196 NAOKI SUGITA
the controls from the same litter, and it gives for each group, underfed and controls, the average brain weight and the corrected cortical thickness in the sagittal and frontal sections of the brain, together with the average thickness. The data for obtaining the correction-coefficient are given in the full table for each individual, but in the condensed table 6 orily the average values of the correction-coefficients for each group appear. The application of the correction-coefficient was made in the way formerly described (Sugita, '17 a). The horizontal sections of underfed brains were not prepared for this study.
Table 6 shows also a comparison of the average thickness of the cortex in the underfed young with that for the standard Albino of the same brain weights. As the present study was not extended to the horizontal sections, the average thickness of the cortex was determined from only the two kinds of sections from the same individual and it was compared with the corresponding average for the standards. In the standards, these values proved to be within 0.5 per cent of the general average thickness of the cortex based on the three kinds of sections. Here, in table 6, the standard values were obtained from the somewhat smoothed curve based on the data formerly presented (table 9 and chart 9, Sugita, '17a).
Table 6 a (unpubhshed) for the sagittal section showed for the underfed that the cortical thickness at the frontal pole (locality I) is evidently very much greater than that of the controls or the corresponding standard value for the same brain weight, comparison having been made on the basis of the data given formerly (table 6 and chart 4, Sugita, '17 a). Locality II was the next which exceeds in the cortical thickness on the side of the underfed. Localities III and IV stand in general slightly in favor of the underfed, but at locality V, the occipital pole, there was found no notable difference in the cortical thickness between the underfed and the standard. As a rule, the cortical thickness of the normal Albino diminishes from the frontal to the occipital pole — from locality I to locality V — and the cortex at the frontal pole increases most rapidly in the early age. This is also just the order of the excesses in the cortical thickness of the underfed
GROWTH OF THE CEREBRAL CORTEX 197
when compared with the standard values for the brains weighing the same. The cortical thickness at each locality of the controls was on the average fairly in accord with the standard (the detailed evidence for these conclusions is contained in table 6 a, not here published).
In table 6 b (unpublished), in which the cortical thickness at localities VI, VII, and VIII of the frontal section was given, it was also clearly seen that the localities VI and VII are much greater in the cortical thickness, compared with those of the controls or the standard values of the same brain weight. The excess amounts on the average to more than 10 per cent. The locality VIII, at which the cortex is heterogeneous in laminar structure, did not show any significant difference in the cortical thickness, compared with the normal, though in some cases here and there it was found somewhat thicker in the underfed (the evidence for these determinations is contained in table G b, not here published).
One more notable thing found in the cerebral cortex of the underfed was that, while in the controls and standards the locality VII is always somewhat greater in thickness than the locality VI, the relation has, in many cases (18 out of 44) of the underfed, proved to be reversed (A a, h; B i; C a, c; D d, e; E c, h; F b, c, f, h; G a, c, g, e and h).
Generally considered, the localities which are situated nearer to the ventricular wall, the locus of the cell division, seem to have gained much more in the cortical thickness in the case of the underfed, while the localities remote from the matrix (for example, locality V) or the part constructed heterogeneousl}^ (for example, locality VIII) appear to be modified but little by underfeeding.
As is to be seen in table 6, the average thickness of the cortex is in favor of the underfed Albinos. If compared with the standard values for the same brain weight, the average cortical thickness in the underfed young (table 6) is greater than tjie standard on the average by 7 per cent (average of all eight litters, T. groups only), while t^e controls are greater on the average by only 1.8 per cent (average of Litters A to E^ C. groups only). According
TABLE 6 Giving for each litter group in this study the average age, brain weight, and the average cortical thickness in the sagittal and frontal sections. The general average cortical thickness was obtained and compared with the standard value for the same brain weight, quoted from a previous paper (Sugita, '17a). The data for each individual and for each locality of the cortex were originally tabulated in three full tables (tables 6a, 6b and 6c) which are on file at The Wistar Institute and from which this table 6 was condensed. The correction-coefficients are given in averages for each litter group for each kind of section. The averages for the test and control groups are given at the end of the table.
TEST CONTROL
AVERAGE AGE
AVERAGE BRAIN WEIGHT
SAGITTAL SECTION
FRONTAL SECTION
AVERAGE
SERIES, LITTER AND GRODP
Correction coefficient
Cortical thickness
Correction
coefficient
Cortical
thickness
Cortical
thickness
Standard for the same brain weight
days
grams
mm.
mm.
mm.
mm.
Series I
A c, a, d, f
T.
7
0.584
1.16
1.24
1.18
1.47
1.35
1.'9
h
T.
15
1.024
1.21
1.64
1.28
2.05
1.85
1.73
> b, g
C.
8
0.688
1.09
1.34
1.14
1.46
1.40
1.38
i
C.
17
1.278
1.23
1.77
1.26
2.00
1.89
1.84
Series I
B a, c, e, f
T.
9
0.644
1.12
l..;3
1.17
1.53
1.43
1.40
i
T.
19
1.052
1.20
1.66
1.37
2.15
1.91
1.74
b, d
C.
6
0.543
1.08
1.18
1.09
1.32
1.25
1.25
g, h, j
C.
18
1.144
1.24
1.74
1.31
2.01
1.88
1.80
Series I
C a, c, d
T.
20
1.105
1.17
1.74
1.25
2.08
1.91
1.77
b, e
C.
22
1.307
1.17
1.76
1.16
1.97
1.87
1.85
Series I
D a, c, d
T.
12
0.778
1.15
1.54
1.24
1.89
1.72
1.61
e
T.
18
1.089
1.17
1.73
1.28
2.10
1.92
1.77
b
C.
9
0.870
1.13
1.55
1.22
1.87
1.71
1.67
f
C.
22
1.220
1.14
1.78
—
—
1.82
Series I
E b, c, d ,
T.
12
0.867
1.11
1.53
1.23
1.95
1.74
1.66
g, h
T.
20
1.122
1.20
1.81
1.26
2.15
1.98
1.79
e, f
C.
II
17
1.179
1.10
1.68
1.21
1*94
1.81
1.79
GROWTH OF THE CEREBRAL CORTEX
199
TABLE 6
-Continued
TEST CONTROL
AVERAGE AGE
AVERAGE BRAIN WEIGHT
SAGITTAL SECTION
FRONTAL SECTION
AVERAGE
SERIES, LITTER AND GROUP
Correction coefficient
Cortical thickness
Correction coefficient
Cortical
thickness
Cortical thickness
Standard for the same brain weight
days
grams
mm.
mm.
mm.
mm.
Series II
Fa, b
T. I
13
0.832
1.17
1.57
1.21
1.8
1.72
1.62
c-1
T. II
25+
1.204
1.24
1.81
1.32
2.15
1.98
1.82
Series III
Ga-g
T. I
11 +
0.844
1.14
1.55
1.24
1.89
1.72
1.63
h-j
T. II
22
1.154
1.19
1.78
1.26
2.15
1.97
1.80
Average 1
T. I
11
0.758
1.14
1.46
1.21
1.77
1.61
1.54
(Her. I-III) j
T. II
20
1.107
1.20
1.74
1.29
2. 2
1.93
1.77
Average 1
C. I
8
0.700
1.10
1.36
1.15
.55
1.45
US
(Ser. I) /
C. II
19+
1.226
1.18
1.75
1. 4
1.98
1.86
1.82
to table 6 c (unpublished), which gives comparisons of cortical thickness of the underfed with the standard in each section, the average cortical thickness in the sagittal section of the underfed exceeds the standard on the average by 5.3 per cent and that in the frontal section of the underfed on the average by 8.7 per cent.
8. Area of the Cortex in the Sagittal and Frontal Sections
Following the procedures which have been described earlier for the measurement of the area of the cortex in the sagittal and frontal sections of the Albino brains (Sugita, '18 b), the data for the underfed Albinos were obtained. Table 7 presents in condensed form for each group the averaged data on the corrected area of the cortex together with the average correction-coefficient for each group, in the sagittal and frontal sections, respectively. The observed data, as measured on the slides, and the data for correction-coefficient for each individual were tabulated in tables 7 a and 7 b (unpublished), on the basis of which table 7 was made. In table 7 (and in table 7 b) the total areas of the frontal sections (one hemicerebrum) and the percentage of the cortical area to the total area of the section are also entered.
200
NAOKI SUGITA
TABLE 7
Giving for each litter group in this study the average brain weight, the corrected areas of the cortex in the sagittal and frontal sect'ons, and the total area of the frontal section and the average correction-coefficients for each group for each kind of section. The percentage values of the cortical area to the area of the total section in the frontal section are also given for each group. This table was condensed from two detailed tables for individual observed data and the data for the correction-coefficients. The averages for the test and control groups are given at the foot of the table
TEST CONTROL
AVERAGE
BRAIN WEIGHT
SAGITTAL SECTION
FRONTAL
SECTION
SERIES, LITTER AND GROUP
Correction-coefficient
Area of cortex
Correction-coefficient
Area of cortex
Total area of section
Percentage of cortical area to the total
area
grams
mm."
mm,.
mm.
per cent
Series I
A c, a, d, f
T. I
0.584
1.16
14.6
1.18
13.4
28.8
45
h
T. II
1.024
1.21
22.2
1.28
22.8
45.0
51
b, g
C. I
0.688
1.09
17.4
1.14
15.2
31.9
46
i
C. II
1.278
1.23
27.4
1.26
21.7
43.6
50
Series I
B a, c, e, f
T. I
0.644
1.12
16.9
1.17
15.0
31.6
47
i
T. II
1.052
1.20
23.3
1.37
23.4
45.7
51
b, d
C. I
0.543
1.08
9.1
1.09
11,6
25.1
46
g, h, j
C. II
1.144
1.24
24.6
1.31
21.7
45.3
47
Series I
C a, c, d
T. II
1 . 105
1.17
24.5
1.25
22.0
43.6
50
1), e
C. II
1.307
1.17
27.8
1.16
22.2
46.0
48
Series I
D a, c, d
T. I
0.778
1.15
19.4
1.24
17.9
36.1
50
e
T. II
1.089
1.17
24.2
1.28
20.0
41.0
49
b
C. I
0.870
1.13
20.6
1.11
18.7
38.8
48
f
C. II
1.220
1.14
26.7
—
—
—
—
Series I
•
E b, c, d
T. I
0.867
1.11
19.9
1.23
19.8
38.4
52
g. h
T. II
1.122
1.20
25.9
1.26
23.4
45.9
51
e, f
C. II
1.179
1.10
24.2
1.21
22.2
45.2
49
Series II
F a, b
T. I
0.832
1.17
20.8
1.21
18.6
38.0
50
c-I
T. II
1.204
1.24
26.0
1.32
23.4
47.3
50
GROWTH OF THE CEREBRAL CORTEX
201
TABLE l^Continued
TEST CONTROL
AVERAGE
BRAIN WEIGHT
SAGITTAL
SECTION
FRONTAL
SECTION
SERIES, LITTER AND GROUP
Qorrection-coefficient
Area of cortex
Correction-coefficient
Area of cortex
Total area of section
Percentage of
cortical
area to
the total
area
grams
mm 2
mm.
mm .
per cent
Series III
G a-ig
T.
I
0.844
1.14
20.1
1.24
19.2
38.5
50
h-j
T.
II
1.154
1.19
25.6
1.26
22.9
46.2
50
Average 1
T.
I
0.758
1.14
18.6
1.21
17.3
35.2
49
(Ser. I-III)j
T.
II
1.107
1.20
24.5
1.29
22.6
45.0
50
Average \
C.
I
0.700
1.10
15.7
1.15
15.2
31.9
48
(Ser. I) /
C.
II
1.226
1.18
26.1
1.24
22.0
45.0
49
The above-mentioned corrected data for each individual were separately paired with the corresponding standard values for the same brain weight, quoted from my previous study (Sugita, '18 b) in table 8 a (unpul)lished) and from this latter table 8 was condensed, giving only the averages for each group.
Briefly stated, the area of the cortex in the sagittal section of the underfed is on the average greater by 1.4 per cent (average of all eight litters, T. groups only) than in the standard, while the controls are on the average about 1.9 per cent less than the standard.
The average area of the total frontal section is in the underfed greater than that of the standard by 2.4 per cent (average of all eight litters, T. groups only), while the controls are less by 3.8 per cent (average of Litters A to E, C. groups only) than the standard, and the area of the cortex in the frontal section is in the . underfed greater on the average by 5.0 per cent, while in the controls less by 2.1 per cent, than the standard (table 8). From these observations, it may be easily concluded that in the underfed the proportion of the cortex to the total section is higher than in the standard or control, as shown by the percentage values directly calculated for each brain (table 7 b) and given in a condensed form in the last column of table 7, where the values are
202
NAOKI SUGITA
TABLE 8
Giving for each litter group in this study the average brain iveight, the corrected areas of the cortex in the sagittal and frontal sections, and the area, of the entire frontal section, respectively, compared tvith the corresponding standard values for the same brain weight. The standard values are all entered according to my previous presentation (Sugita, '18b). This table was condensed from an original complete table 8a for each individual. The averages for the test and control groups are given at the end of the table.
AVER
SAGITTAL SECTION
FRONTAL SECTION
Area of cortex
Tota
area
Area of cortex
SERIES, LITTER AND
AGE
BRAIN
WEIGHT
GROUP
Corrected
Stan^^ard
Area
Corrected
Standard
Corrected
Standard
Area
Thick
Thick
ness
ness
grams
mm.
mm.
mm.
mm. 2
mm.
wm.2
mm.'
mm.
Series I
A c, a, d, f
0.584
14.6
13.8
11.4
28.8
28.3
13.4
12.9
8.9
h
1.024
22.2
23.0
13.5
45.0
42.0
22.8
20.7
11.1
b, g
0.688
17.4
16.0
12.6
31.9
31.8
. 15.2
15.0
10.1
i
1.278
27.4
26.7
15.5
43.6
48.5
21.7
23.0
10.9
Series I
B a, c, e, f
0.644
16.9
15. Jt
12.5
31.6
30.4
15.0
14.2
9.6
i
1.052
23.3
23.6
14.0
45.7
43.0
23.4
21.0
10.9
b, d
0.543
13.1
13.0
11.0
25.1
28.3
11.6
11.9
8.6
g, h, j
1.144
24.6
25.2
14.1
45.3
45.2
21.7
21.7
10.8
Series I
C a, c, d
1.105
24.5
2Jt.h
14.0
43.6
44.1
22.0
21.5
10.6
b, e
1.307
27.8
27.1
15.8
46.0
49.3
22.2
23.3
11.3
Series I
D a, c, d
0.778
19.4
18.9
12.6
36.1
34-8
17.9
17.0
9.5
e
1.089
24.2
24.5
14.0
41.0
44-0
20.0
21.3
9.5
b
0.870
20.6
20.5
13.3
38.8
38.0
18.7
18.8
10.0
f
1.220
26.7
26.0
15.0
—
47.0
—
22.5
—
Series I
E b, c, d
0.867
19.9
20.3
13.0
38.4
37.5
19.8
18.7
10.1
g, h
1.122
25.9
25.0
14.3
45.9
44.5
23.4
21.5
10.9
e, f
1.179
24.2
25.3
14.4
45.2
46.0
22.2
23.6
11.4
GROWTH OF THE CEREBRAL CORTEX 203
TABLE 8— Continued
AVER
SAGITTAL SECTION
FRONTAL SECTION
Area of cortex
Tota
area
Area of cortex
SERIES, LITTER AND
AGE
BRAIN
WEIGHT
GROUP
Corrected
Sttt7ld ard
Area
Corrected
Standard
Corrected
Standard
Area
Thick
Thick
ness
ness
grams
mm. 2
nim.
mm.
m,m.'
mm."
mm. 2
m.m.
TOTO.
Series II
F a, b
0.832
20.8
19.4
13.2
38.0
36.5
18.6
17.9
9.9
c-1
1.204
26.0
25.9
14.4
47.3
46.7
23.4
22.3
10.9
Series III
Ga-g
0.844
20.1
19.8
13.0
38.5
36.9
19.2
18.2
10.2
h-j
1.154
25.6
25.7
14.3
46.2
45.3
22.9
21.9
10.7
Average 1 (T. I)
0.758
18.6
17.9
12.6
35.2
34-1
17.3
16.5
9.7
(Ser. I-III)/ (T.II)
1.107
24.5
24.6
14.1
45.0
44-2
22.6
21.5
10.7
Average\ (C. I)
0.700
15.7
16.5
12.3
31.9
32.7
15.2
15.2
9.6
(Ser. I) / (C. II)
1.226
26.1
26.1
15.0
45.0
47.2
22.0
22.8
11.1
higher on the average by 3 per cent (1 to 4 per cent in individual cases) than the standard or controls. These results fit with the observation that in the underfed the cortical thickness in the frontal section is 8.7 per cent greater than for the standard (chapter 7).
9. COMPUTED VOLUME OF THE CORTEX
In a former paper (Sugita, '18 b), it was assumed that, as the form of the cerebrum of the albino rat is relatively simple and nearly constant, the relative volumes occupied by the cortical cells could be computed, and compared among themselves, by reducing the data obtained by measurement to a simple geometrical form, since the cortical areas in the sagittal and frontal sections stand in fixed relations to the respective diameters L.F and W.D and to the cortical thickness of the sections from the same brain. These relations have been expressed as follows (Sugita, '18 b):
204 NAOKI SUGITA
Cortical area (mm.-) in sagittal section
L.F (mm.) ^ constant (1)
Cortical thickness (mm.) in the same
Cortical area (mm.-) in frontal section ^rr t^ / x , , .^s
-7s — T- — 1 xi- r } w — Til -=- **^ Mimm..) = constant (2)
Cortical thickness (mm.) m the same ^ ^
And the computed volume of the cortex should be obtained simply by the following formula :
L.F X W.D X T (ah in millimeters), (3)
where T gives the general average thickness of the cerebral cortex of the same brain.
As shown in table 9, which has been condensed from table 9 a (unpublished) for each individual, the constant ratios obtained by the above formulas (1) and (2) fall between 1.10 and 1.29 for the sagittal sections and between 0.80 and 0.95 for the frontal sections, throughout both the underfed and the control groups. The averages of the ratios for the sagittal and frontal sections of the underfed are, respectively, 1.18 and 0.88, and those of the controls are, respectively, 1.20 and 0.88. I have previously given the figures 1.22 and 0.91, respectively, as these ratios of the standard albino rat brains weighing more than 0.5 gram. So it may be assumed that the ratios are nearly the same in both the underfed and the controls; slight differences in the underfed from the standard may be regarded as due to the facts that the cerebrum of the underfed is slightly more elongated and the cortical thickness is somewhat greater than in the standard. As the product of the coefficients in the underfed (I'.IS X 0.88) falls somewhat lower than that in the standard (1.22 X 0.91), the results of L.F X W.D X T should be about 5 per cent higher in the underfed than in the standard.
The relative volumes of the cortex, obtained by the formula (3), are computed and given in table 11 (without any special correction), compared with the corresponding standard values for brains of the same age, instead of for brains of the same weight. The relative volume of the cortex in the underfed brains, which are considerably retarded in total weight development, is greater than for the standard brains of the .same weight, which are necessarily younger and less developed as regards the cortical elements than the underfed brains of like weight.
GROWTH OF THE CEREBRAL CORTEX 205
Since in the underfed the average cortical thickness in the sagittal and frontal sections was used in place of the standard T, based on the thickness of the sagittal, frontal and horizontal sections (compare Sugita, '17 a), therefore corresponding values of T have been used in calculating the standard values for the present comparison.
For this comparison, the test animals may be considered in two groups, T. I and T. II. In T. I groups, in which all test rats have a brain weight less than 1.0 gram, the average computed volume of the cortex is less than the standard by 16 per cent, while in T. II groups, which contain the test rats with brains weighing above 1.0 gram, it is more than the standard on the averagfe by 1 per cent. On the other hand, the cortical volume in C. I groups, which embraces the controls having brain weights less than 1.0 gram, is on the average 2.4 per cent less, and in C. II groups, the controls with brain weights above 1.0 gram, it is on the average 7.5 per cent more than the standard for the same age (table 11, last lines). As these comparisons are based on the numbers obtained by calculation and not on the direct measurement, slight discrepancies cannot be regarded as significant, and, as already noted, the results in the underfed are open to special correction of a few per cent for an accurate comparison.
The underfed brains are much retarded in the weight development and the brains weighing up to 1.0 gram include those of ages up to sixteen days, at which age the normal rats have a brain weight 10 per cent heavier than the test rats (chapter V). We conclude, therefore, that, calculated by the formula L.F X W.D X T, the relative volumes of the cortex in the underfed are nearly the same as in the standard in the brains weighing more than 1.0 gram (T. II groups), while, on the contrary, they are considerably smaller than the standard in the case of the brains weighing under 1.0 gram or under the age of sixteen days, if the age be taken as the standard of comparison.
It appears, therefore, that in rats underfed severely the cortical volume is considerably retarded in growth during the early period of development, but this is probably fairly compensated later when the brain attains a weight of more than 1 .0 gram or an age
206
NAOKI SUGITA
TABLE 9
Giving for each litter group in this study the average brain weight, the measurements L.F and W.D, the quotient of the cortical area divided by the cortical thickness {given also in table 8), and the ratio of the latter to the measurement L.F or W .D, for the sagittal and frontal sections. The width-length index which is obtained by {W .D X 100)/L.F is also given. This table was condensed from an U7ipublished table 9a for each individual. The averages for the test and control groups are given at the foot of the table. The ratios given in this table 9 are based on the average of the individual ratios a7id not on those obtained directly from the average L.F or W.D and the average quotients
H
CORT.
CORT.
TEST CONTROL
<
m a <
AVERAGE BRAIN WEIGHT
L.F
.\REA
RATIO
W. D
AREA
RATIO
z
SERIES, LITTER AND GROrP
CORT.
THICKN.
IN
SAGITTAL
CORT. THICKN.
IN FRONTAL
is
•<:
SECTION
SECTION
^
days
grams
mm.
7nm.
mm.
mm.
Series I
A c, a, d, f
T.
7 —
0.584
9.28
11.4
1.23
9.88
8.9
0.89
106
h
T.
II
15
1.024
11.85
13.5
1.14
12.00
11.1
0.93
101
b, g
c.
8
0.688
9.90
12.6
1.27
10.60
10.1
0.95
107
i
c.
II
17
1.278
12.95
15.5
1.20
12.85
10.9
0.84
-99
Sey-ies I
B a, c, e, f
T.
9
0.644
9.70
12.5
1.29
10.46
9.6
0.92
108
i
T.
II
19
1.052
12.10
14.0
1.16
12.45
10.9
0.88
103
b, d
C.
6
0.543
8.78
, 11.0
1.24
9.85
8.0
0.88
112
g, h, J
C.
II
18
1.144
12.28
14.1
1.16
12.40
10.8
0.87
101
Series I
C a, c, d
T.
II
20
1.105
12.32
14.0
1.14
12.17
10.6
0.87
99
h, e
C.
II
22
1.307
13.30
15.8
1.19
12.98
11.3
0.87
98
Series I
D a, c, d
T.
12
0.778
10.90
12.6
1.15
10.77
9.5
0.88
99
e
T.
II
18
1.089
12.25
14.0
1.14
11.85
9.5
0.80
97
b
C.
9
0.870
10.95
13.3
1.21
11.45
10.0
0.82
104
f _
C.
II
22
1.220
12.40
15.0
1.21
12.80
—
—
103
Series I
E b, c, d
T.
12
0.867
10.65
13.0
1.22
11.30
10.1
0.90
106
g, h
T.
II
20
.1.122
12.10
14.3
1.19
12.35
10.9
0.88
102
e, f
C.
II
17
1.179
12.23
14.4
1.18
12.48
11.4
0.92
102
GROWTH OF THE CEREBRAL CORTEX
207
TABLE Q— Continued
»
CORT.
CORT.
SERIES, LITTER AND GROUP
TEST CONTROL
o
<;
H
<
AVERAGE BRAIN WEIGHT
L.F
AREA
CORT.
THICKN.
IN SAGITT.\L
RATIO
W. D
AREA COKT.
THICKN. IN
FRONTAL
RATIO
m 1 X
Q 2
>
<
SECTION
SECTION
?
days
grams
mm.
mm.
mm.
mm..
Series II
F a, b
T.
I
13
0.832
11.18
13.2
1.19
11.23
9.9
0.88
101
c-1
T.
II
25+
1.204
12.66
14.4
1.14
12.30
10.9
0.88
97
Series III
Ba-g
T.
I
11 +
0.844
10.99
13.0
1.18
11.22
10.2
0.90
102
h-j
T.
II
22
1.154
12.58
14.3
1.14
12.20
10.7
0.87
97
Average 1
T.
I
11
0.758
10.45
12.6
1.21
10.81
9.7
0.90
104
(Ser. I-III)/
T.
II
20
1.107
12.27
14.1
1.15
12.19
10.7
0.87
99
Average \
C.
I
8
0.700
9.88
12.3
1.24
10.63
9.6
0.88
108
(Ser. I) /
C.
II
19+
1.226
12.63
15.0
1.19
12.70
11.1
0.88
101
of more than sixteen days, so that after this period there is no longer any significant difference in the cortical volumes between the test and the standard animals.
10. NUxMBER OF NERVE CELLS IN THE CEREBRAL CORTEX •
The actual number of nerve cells in the frontal cortex in a unit volume of 0.001 mm,^, or 0.1 mm.^ in area on the shde by 10 micra in thickness, was counted in the lamina pyramidalis and in the lamina ganglionaris at locality VII, the middle part of the cortical band of the frontal section. The procedure for counting the cell number, adopted by me for the standard values and described in my previous paper (Sugita, '18 b), has been strictly followed here also. The number of cells in the lamina pyramidalis and the lamina ganglionaris and the number of the ganglion cells in a unit volume have been recorded and then converted into the number of cells in the same unit volume in the fresh condition of the brain by the use of the correction-coefficients based on observations. All the data have been tabulated in table 10 a (unpublished) and condensed in table 10 for each group. The
208
NAOKI SUGITA
TABLE 10
Givitig for each litter group in. this study the average age, hraiti, weight, correctioncoefficient, and the corrected number of nerve cells in a unit volume {0.001 mm.^) in the lamina pyramidalis and the lamina ganglionaris and the corrected number of ganglion cells only in the same volume, measured at locality VII. This table was condensed from a detailed table, table 10a (unpublished), which gives the same data for the individual cases. The averages for the test and qpntrol groups are given at the foot of the table.
TEST
AVERAGE
AVERAGE
CORRECTION
NUMBER OF CELLS IN
0.001 mm.'
GROUP
CONTROL
AGE
WEIGHT
COEFFI
Lamina
Lamina
Ganglion
CIENT
pvrami
gansjlio
cells in
dalis
nans
lam. gangl.
days
grams
Series I
•
A c, a, d, f
T. I
7 —
0.584
1.18
271
167
47
h
T. II
15
1.024
1.28
120
86
21
b, g
C. I
8
0.688
1.14
224
131
40
i
C. II
17
1.278
1.26
107
75
20
Series I
B a, c, e, f
T. I
-9
0.644
1.17
232
132
39
i
T. II
19
1.052
1.37
117
77
19
b, d
C. I
6
0.543
1.09
268
177
58
g, h, i
C. II
18
1.144
1.31
109
76
21
Series I
C a, c, d
T. II
20
1.105
1.25
109
73
20
b, e
C. II
22
1.307
1.16
109
79
26
Series
D a, c, d
T. I .
12
0.778
1.24
152
90
21
e
T. II
18
1.089
1.28
118
81
18
b
C. I
9
0.870
1.22
152
93
27
f
C. II
22
1.220
1.14
111
75
22
Series I
E a, b, c, d
T. I
12
0.835
1.21
144
101
25
g, h
T. II
20
1.122
1.26
116
79
21
e, f
C. II
17
1.179
1.21
116
79
23
Series II
Fa, b
T. I
13
0.832
1.21
162
98
29
c-1
T. II
25+
1.204
1.32
105
74
19
GROWTH OF THE CEREBRAL CORTEX
209
TABLE 10— Continued
TEST CONTROL
AVERAGE AGE
AVERAGE
BRAIN WEIGHT
CORRECTION COEFFICIENT
ND.MBER OP CELLS IN 0.001 mm.^
GROUP
Lamina
pyrami dalis
Lamina
ganglio naris
Ganglion
cells in
lam.gangl
Series III Ga-g
days
T. I T. II
grams 11 +
22
0.844
1.154
1.24 1.26
149 108
94 80
24 20
Average ) (Ser. I-III)/
Average ) (Ser. I) /
T. I T. II
C. I C. II
1120 819+
0.753 1.107
0.700 1.226
1.21 1.29
1.15 1.24
185 113
215 110
, 114
79
134
77
31 20
42 22
sum of the cell numbers in the lamina pyramidalis and the lamina ganglionaris, which may be regarded as representing the average cell density in the cerebral cortex, are also given in table 11, as A^, and compared with the corresponding standard values for the brains of the same age, taken from a former paper (Sugita, '18 b). When compared in this way, it is seen that the observed cell number in a unit volume is generally higher than the standard in brains which weigh less than 1.0 gram (T. I groups). The excess in cell number in underfed brains weighing less than 1.0 gram (T. I groups) is on the average 17 per cent, and that of the control brains weighing less than I.O gram (C. I groups) is on the average about 7 per cent. On the other hand, the average cell number of the underfed brains weighing more than 1.0 gram (T. II groups) is almost equal to, while that of the control brains weighing more than 1.0 gram (C. II groups) is less by 4 per cent than, the standard for the same age. The underfed brains are underdeveloped in weight and the brains weighing less than 1.0 gram (T. I groups) contain those of ages up to sixteen days. These relations lead me to conclude that, in the underfed brains weighing less than 1.0 gram or under sixteen days in age, the cell density denoted by A^ (the average cell number in two unit volumes) is distinctly high, when compared with the normal brains of the same age, probably because the brain size or weight
THE JOURNAL OF COMPARATIVE NEUROLOGY, VOL. 29, NO. 3
210 NAOKI SUGITA
or the cortical volume is relatively undeveloped in comparison with the cell number (see above) . In older brains weighing more than 1.0 gram or of ages above sixteen days, these discrepancies have been somewhat balanced, but, when compared with the controls, the underfed brains remain generally slightly higher in the cell density even in rats of sixteen days or older.
Considered in relation to the facts presented in the previous chapter showing that the computed volume of the cortex is below the standard in the underfed brains weighing less than 1.0 gram, it may inferred that the underfed brains, underdeveloped in weight and size, have a relatively higher cell density, because the normal number of cells is crowded into a cortex of smaller total volume.
11. RELATIVE VALUE OF THE COMPUTED NUMBER OF CELLS IN THE ENTIRE CORTEX
As previously shown (Sugita, '18 b), the computed number of nerve cells in the entire cortex may be obtained and the values compared among themselves by the use of the following formula :
N X L.F X W.D X T {L.F, W.D and T, in millimeters),
where N means the relative cell density represented by the sum of the cell numbers in the unit volume in the lamina pyramidalis and in the lamina ganglionaris (that is, the number in two unit volumes), given in table 11, based on table 9, and L.F X W.D X T is the computed volume of the cortex, as already given in the foregoing chapter.
In table 11, these relative values for the volume of the cortex and for the cell number in the cortex in the underfed Albinos are given for each group, each paired with the corresponding standard values for brains of the same age, all condensed from table 11a (unpublished), which gives the corresponding data for each individual. Every standard value was taken from my previous presentation (Sugita, '18 b). Throughout the underfed and the controls, these pairs of figures seem to be nearly in accord, showing on the average only 1.7 per cent excess in the underfed and 3,4 per cent excess in the control brains (average
GROWTH OF THE CEREBRAL CORTEX 211
of all groups), as compared with the standards. As alreadynoted in chapter 9, the results obtained by the use of formulas are open to some error, and in addition the results in the underfed are subject to special correction of a few per cent for a fair comparison, so that the differences recorded may be regarded as probably insignificant and the computed cell number in the entire cortex of the underfed may presumably be considered as equal to the standard number for brains of the same age. If this is so, the process of the cell division in the cerebrum during early life must have been going on undistui"bed even by the severe underfeeding, though both the size and the weight of the brain have been arrested in development by this, in some cases very considerably.
12. Size of Nerve Cells
The standard size of the pyramids (in the lamina pyramidalis) and the ganglion cells (in the lamina ganglionaris) in the cerebral cortex of the albino rats at different ages was presented in my sixth paper (Sugita, '18 c). In the present study on the influence of the severe underfeeding upon the growth of the cerebral cortex, the size of the nerve cells in the cortex was also determined bj^ the measurement of the transverse and longitudinal diameters of the cell body and the nucleus in the pyramids (in the lamina pyramidalis) and in the ganglion cells (in the lamina ganglionaris) at locality VII in the frontal section, in the same manner as for the standard determinations (Sugita, '18 c). The results have been tabulated in table 12 a (unpublished) and condensed in table 12 for each group. The average diameters of the cell body and of the nucleus are obtained by extracting the square roots of the respective products of the transverse by the longitudinal diameters, and these have been corrected, by applying the correction-coefficient, to the fresh condition of the brain. The corrected average diameters have been tabulated in table 13 a (unpublished), compared respectively with the corresponding standard values for the brains of the same age, and condensed in table 13. The correction-coefficients which were used are given in table 12.
TABLE 11
Giving for each litter group in this study the average hrain weight, the age, the computed cortical volume, the cell density and the computed number of cells in the entire cortex, as based on the observed measurements presented in this paper, each compared with the corresponding standard values for the same age. Standard values were taken from my previous presentation (Sugita, '18b). This table was condensed from an original full table 11a {unpublished) , which gives the data for each individual. At the end of the table the averages for the test and control groups are given.
TEST CONTROL
AVERAGE AGE
AVER AGE
BRAIN
WEIGHT
CORTICAL volume:
L.F X W.D X T
cell density:
N
CELL number: N XL.FX W.D XT
GEO UP
Starved
and control^
Standard
for the same age
Starved
and controls
Standard
for the same age
Starved
and controls
Standard for the same age
days
grams
mm J
OTTO. 3
Series I
A c, a, d, f
T.
I
7 —
0.584
134.4
151.8
437
375
482.9
450.8
h
T.
II
15
1.024
263.1
265.0
206
202
542.0
535.0
b, g
C.
I
8
0.688
159.9
165.0
355
354
452.4
467.5
i
C.
II
17
1.278
314.5
275.0
182
198
572.4
545.0
Series I
B a, c, e, f
T.
I
9
0.644
151.6
187.0
364
298
489.1
479.2
i
T.
II
19
1.052
287.7
285.0
194
191
558.1
544-0
b, d
C.
I
6
0.543
112.4
126.5
445
388
457.8
44s. 5
g, h, j
C.
II
18
1.144
285.5
278.3
184
195
526.2
543.3
Series I
C a, c, d
T.
II
20
1.105
287.3
284.7
182
191
521.6
542.0
b, e
C.
II
22
1.307
320.9
289.5
188
188
603.4
540.5
Series I
D a, c, d
T.
I
12
0.778
201.1
238.3
242
213
486.4
505.3
e
T.
II
18
1.089
278.7
280.0
199
195
554.6
546.0
b
C.
I
9
0.870
214.4
207.0
245
230
525.3
476.0
Series I
E b, c, d
T.
I
12
0.867
210.3
249.3
238
207
497.1
516.7
g, h
T.
II
20
1.122
295.9
290.0
194
188
574.0
545.0
e, f
C.
II
17
1.179
278.0
272.5
195
197
535.9
535.0
GEOWTH OF THE CEREBRAL CORTEX
213
TABLE n— Continued
TEST CONTROL
AVERAGE AGE
AVER AGE
BRAIN
WEIGHT
CORTICAL VOLUME
L.F X W.D X T
CELL density:
N
CELL number:
NXL,FX
W.D X T
GROUP
Starved
and controls
Standard for the same
Starved
and controls
standard for the same
Starved
and controls
standard for the same
age
age
age
days
grams
rnm.^
mm.^
Series II
Fa, b
T.
I
13
0.832
218.7
252.5
260
206
550.4
520.0
c-1
T.
II
25+
1.204
307.9
SOS 4
178
180
548.7
545.7
Series III
Ga-g
T.
I
11 +
0.844
213.2
229.1
248
225
520.4
504.1
h-j
T.
II
22
1.154
302.2
294.7
189
186
570.3
546.7
Average 1
T.
I
11
0.758
188.2
218.0
298
254
504.4
496.0
(Ser. I-III)/
T.
II
20
1.107
289.0
286.1
192
190
552.8
543.5
Average 1
C.
I
8
0.700
162.2
166.2
348
S24
478.5
^62.3
(Ser. I) /
C.
II
19
1.227
299.7
278.8
187
195
559.5
541.0
By comparing the corrected values in the underfed with the standard values, the average diameters of the cell body and of the nucleus in the underfed brains are found to be generally smaller, on the average, by 9.8 per cent (cell body by 8.6 per cent and nucleus by 11.0 per cent) than the standard value. At the end of the following table 13 appears a summary of the comparisons, arranged as in the earlier tables in this study.
As seen in this summary, both the pyramids and the ganglion cells are much retarded in development in size of the cell body in the underfed brains weighing less than 1.0 gram or of ages under sixteen days, the average diameters of the cell body being 11.5 per cent (in the pyramids 11.2 per cent and in the ganglion cells 11.8 per cent) smaller than the standard for the same age. But in the underfed brains weighing more than 1.0 gram, this arrest in size-development of nerve cells is no longer so notable, the average diameters of the cell body being smaller than the standard by only 5.7 per cent (in the pyramids by 8.3 per cent and in the ganglion cells by 3.1 per cent). The size of the
214
NAOKI SUGITA
TABLE 12
Giving for each litter group in. this study the average brain iveight, the correctioncoefficient, and the observed {not corrected) diameters (transverse and longitudinal) of the cell body and the micleus of the pyramids (in the lamina pyramidalis) and of the ganglion cells (in the lamina ganglionaris), measured at locality VII in the frontal section. This table was condensed from table 12a (tin published) for individual cases. The averages for the test and control groups are given at the foot of the table
m
% o
o
CO < X
k2
<
■z
o
K S
LAMINA PYRAMIDALIS
LAMINA GANGLIONARIS
SERIES, LITTER AND
Cell body diameters
Nucleus diameters
Cell body diameters
Nucleus
diameters
>
s 2
C
q
>
e
03
H
bl 13 O
a
OJ
■a
J
>
1
M
a o
grams
M
M
M
M
li
M
n
Series I
A c, a, d, f
T.
0.584
1.18
11.5
17.2
10.5
11.2
14.8
22.4
13.0
15.6
h
T.
II
1.024
1.28
14.2
19.5
13.3
15.1
19.8
29.2
17.2
19.8
' b, g
C.
0.688
1.14
14.1
19.0
12.9
14.3
18.2
25.8
16.1
18.2
i
C.
II
1.278
1.26
15.2
22.0
14.1
15.5
20.1
30.5
18.0
20.1
Series I
B a, c, e, f
T.
0.644
1.17
13.3
18.8
12.0
13.5
17.2
25.3
16.0
17.5
i
T.
II
1.052
1.37
14.0
20.4
13.4
15.7
19.5
28.3
17.4
19.6
b, d
C.
0.543
1.09
13.9
18.0
12.4
13.6
18.6
24.1
15.6
17.0
g, h, j
C.
II
1.144
1.31
14.7
20.8
14.4
15.4
19.9
30.3
18.3
19.6
Series I
C a, c, d
T.
II
1.105
1.25
14.6
21.3
13.9
14.3
18.8
29.9
17.7
19.3
b, e
C.
II
1.307
1.16
16.0
21.1
14.4
15.3
19.9
30.4
17.8
19.6
Series I
D a, c, d
T.
0.778
1.24
14.3
19.4
12.9
13.8
17.6
27.7
15.4
17.2
e
T.
II
1.089
1.28
14.0
20.0
12.2
14.0
18.3
28.8
16.2
19.4
b
C.
0.870
1.11
16.1
19.8
14.5
15.8
21.1
27.2
18.2
19.8
f
C.
II
1.220
1.14
14.9
21.5
14.2
14.8
19.2
28.6
17.2
18.0
Series I
E a, b, c, d
T.
0.835
1.23
13.5
19.8
12.8 14.3
17.9
28.3
16.0
18.2
g, h
T.
II
1.122
1.26
14.0
20.7
12.5 14.2
19.7
30.7
16.5
18.1
e, f
C.
II
1.179
1.21
15.1
21.7
13.9 15.4
19.2
30.6
17.6
19.2
GROWTH OF THE CEREBRAL CORTEX
215
TABLE 12— Continued
o
|i
<
n
w -< K
« 2
fa
m
u
z
e^
K H
§5
LAMINA PYRAMIDALI8
LAMINA GANGLIONABIB
SERIES, LITTER AND GROUP
Cell body diameters
Nucleus diameters
Cell body diameters
Nucleus diameters
>
C
2
M
C! O
1-1
>
a S
s o
>
c
C
o
>
H
bC
C
o
grams
M
M
M
M
M
M
M
Series I7
F a, b
T. I
0.832
1.21
14.8
19.7
13.6
14.7
19.3
28.6
17.6
19.3
c-1
T. II
1.204
1.32
14.9
21.0
13.7
14.8
19.0
30.0
17.3
19.1
Series III
Ga-g
T. I
0.844
1.24
14.0
19.8
13.1
14.3
17.9
28.4
16.8
18.4
h-j
T. II
1.154 0.753
1.26
13.9
19.8
12.6
13.9
18.3
28.7
16.2
18.1
Average \
T. I
1.21
13.6
19.1
12.5
13.6
17.5
26.8
15.8
17.7
(Ser. I-III) /
T. II
1.107
1.29
14.2
20.4
13.1
14.6
19.1
29.4
16.9
19.1
Average |
C. I
0.700
1.15
14.7
18.9
13.3
14.6
19.3
25.7
16.6
18.3
(Ser. I) /
C. II
1.226
1.22
15.2
21.4
14.2
15.3
19.7
30.1
17.8
19.3
nucleus is much more affected by the underfeeding than that of the cell body. In the underfed brains of T. I groups the average diameter of the nucleus is smaller by 13.9 per cent (in the pyramids by 15.3 per cent and in the ganglion cells by 12.5 per cent) and in those of T. II groups it is smaller by 8.0 per cent (in the pyramids by 11.0 per cent and in the ganglion cells by 5.1 per cent) than the standard for the same age. The deficiency in the average diameter of the cell body by 6 to 12 per cent and that of the nucleus by 8 to 14 per cent correspond to the inferiority in volume of about 20 to 45 per cent and 25 to 50 per cent, respectively.
On the other hand, in the control brains of all weights, the size of the cell body and of the nucleug have proved to be also somewhat smaller than the standards, but the deviations are not so much in comparison with the underfed, the deficiency in the average diameters of the cell body and the nucleus being on the average 5.3 per cent (table 13).
216
NAOKI SUGITA
TABLE 13 Giving for each litter group in this study the average age, brain weight, the corrected average diameters of the cell body and the nucleus of the pyramids {in the lamina pyramidalis) and the ganglion cells {in the lamina ganglionaris), based on the condensed data in table 12, each compared with the corresponding standard values for the same age, taken from my former presentation {Sugita, '18c.) This table was condensed from table Ida {unpublished) for individual cases. The averages for the test and control groups and their percentage relations are given at the end of the table, {per. diff.) = percentage difference
TEST CONTROL
H O <
m o <
> <
» <
a
B
m o <
> <
L.\MIN.\ PYR.A.MID.\.L1S
L.\MIN.\*G.\NGLION.\^RIS
SERIES, LITTER AND
Cell body Aver, diameter
Nucleus Aver, diameter
Cell body Aver, diameter
Nucleus Aver, diameter
1 1
!:
o O
u
■a
a
o3
s
u
-d
a B
m
T3 01
a
S 02
days
grams
M
M
M
M
J"
M
M
M
Series I
Ac, a, d, f
T.
7 —
0.584
16.6
19.4
13.3
16.6
21.6
25.9
16.8
20.7
h
T.
II
15
1.024
21.1
23.7
18.1
19.8
30.6
31.3
23.6
24.4
b, g
C.
8
0.688
18.7
19.6
15.4
16.9
24.7
26.7
19.5
21.2
i
C.
II
17
1.27
23.1
23.8
18.7
20.0
31.2
31.3
2 .1
24.4
Series I
B a, c, e, f
T.
9
0.644
18.4
20.7
14.8
17.8
24.3
27.9
19.4
22.1
i
T.
II
19
1.052
23.2
24.0
19.8
20.0
32.1
31.4
25.1
24.5
b, d
C.
6
0.543
17.4
18.5
14.3
15.8
23.3
24.9
17.8
19.8
g, h, j
C.
II
18
1.144
23.1
23.9
19.7
20.0
32.4
31.3
25.0
24.4
Series I
C a, c, d
T.
II
20
1.105
22.1
23.9
17.6
20.0
29.7
31.4
22.9
24-4
b, e
C.
II
22
1.307
21.4
24.0
17.4
20.0
29.1
31.5
21.8
24.5
Series I
D a, c, d
T.
12
0.778
20.6
22.9
16.6
19.5
27.4
30.1
20.2
23.8
e
T.
II
18
1.089
21.4
23.9
16.8
20.0
29.5
31.3
22.8
24.4
b
C.
9
0.870
21.8
22.1
18.4
18.8
29.3
28.4
23.2
23.0
f
C.
II
22
1.220
22.4
24.1
18.2
20.1
29.5
31.6
22.1
24.5
Series I
E a, b, c, d
T.
X2
0.835
19.8
23.0
16.4
19.8
27.1
30.9
20.7
24-2
g, h
T.
II
20
1.122 21.5
24-0
16.8
20.0
31.0
31.4
21.7
24.5
e, f
C.
II
17
1.179 22.0
23.7
17.7
19.9
29.5
31.3
22.4
24.5
GROWTH OF THE CEREBRAL CORTEX
217
TABLE n— Continued
TEST CONTROL
O <
> <
s
z
a o m o <
LAMINA PYRAMIDALIS
LAMI.VA GANGLIONARIS
SERIES, LITTER
Cell body Aver, diameter
Nucleus Aver, diameter
Cell body Aver, diameter
Nucleus Aver, diameter
1
6
S
5
O
3
1
o
Q
-a c 5
o
■E
-0
a
dans
grams
ij
M
At
M
M
M
Series II
F a, b
T. I
13
0.832
20.8
2S.2
17.1
19.8
28.5
31.1
22.3
H.4
' c-1
T. II
25+
1.204
22.9
23.9
18.6
20.0
31.0
31.5
23.6
H.4
Series III
Fa-g
T. I
11 +
0.844
20.6
22.5
17.0
19.2
27.9
29.9
21.9
23.5
h-j
T. II
22
1.154
21.0
24.1
16.7
20.1
29.0
31.5
21.7
24.5
Average
(Ser. I-III)
T. I
11
0.753
19.5
22.0
15.9
18.8
26.1
29.3
20.2
23.1
(per. diff.)
(-11.2)
(-15.3)
(-11.8)
(-12.5)
Average
(Ser. I-III)
T. II
20
1.107
21.9
23.9
17.8
20.0
30.4
3H
23.1
24.4
(per. diff.)
(- 8.3)
(-11.0)
(- 3.1)
(- 5.1)
Average
- (Ser. I)
C. I
8
0.700
19.3
20.1
16.0
17.2
25.8
26.7
20.2
21.3
(per. diff.)
(- 3.8)
(- 6.7)
(- 3.2)
(- 5.1)
Average)
(Ser. I)
C. II
19+
1.226
22.4
23.9
18.3
20.0 30.3
31.4
23.1
24.5
(per. diff.)
(- 6.2)
(- 8.5)j
(- 3.3)
(- 5.5)
It is also seen that by underfeeding the nucleus is more affected than the entire cell body both in the pyramids (deficiency in diameters; T. I groups: cell body 11.2 per cent and nucleus 15.3 per cent, T. II groups: cell body 8,3 per cent and nucleus 11.0 per cent) and in the ganglion cells (deficiency in diameters; T. I groups: cell body 11.8 per cent and nucleus 12.5 per cent, T. II groups: cell body 3.1 per cent and nucleus 5.1 per cent) of brains of all weights, while the pyramids are more markedly affected than the ganglion cells both in the cell body (deficiency in diameters on the average of T. I and T. II groups: pyramids 9.8 per cent and ganglion cells 7.5 per cent) and in the nucleus (deficiency
218 NAOKI SUGITA
in diameters on the average of T. I and T. II groups: pyramids 13.2 per cent and ganglion cells 8.8 per cent). In young brains which weigh less than 1.0 gram, the influence of the underfeeding is considerable, while in brains weighing more than 1.0 gram or of ages more than sixteen days we can not detect any large arrest in the size-development, especially of the ganglion cells (the sizes of the cell body and the nucleus of the ganglion cells in the T. II groups are quite equal to the corresponding sizes in C. II groups) (tables 12 and 13). These observations are in agreement with the conclusions reached by Morgulis Til).
13. PERCENTAGE OF WATER IN BRAIN
As stated earlier (in chapter III), Litter H in Series II, in which a young primipara mother was entrused with seventeen young in order to produce a series of underfed young, was used partly for the investigation of the percentage of water in the underfed brain and partly for a histological study of myelination (not considered at this time).
In this Series II the development in brain weight is not so greatly arrested, as compared with the arrest in body growth, as in Series I. As already shown, in Litter F, which was treated in a similar manner, the brain weight is on the average 9 per cent low, but in this Litter H it has been possible to arrest the brainweight growth on the average by about 12 per cent, compared with the standard of the same age (compare table 4) .
Table 14 gives for each individual examined in this litter the sex, the age, the brain weight, and percentage of water in the brain, each accompanied by the standard percentage of water contained in the brains of the same age and sex and also of the same weight and sex. The differences are given in special columns.
By obtaining averages, it is found that the underfed brain contains slightly (0.48 per cent) more water, when compared with the normal brain of the same age and somewhat (1.4 per cent) less water, when compared with the normal brain of the same weight. This means in terms of the percentage of water.
GROWTH OF THE CEREBRAL CORTEX
219
TABLE 14
Showing for each brain in litter H the sex, the age, the brain weight, and the percentage value of water in the brain, accompanied with the standard values of percentage of water in brain for the same age and for the same brain weight. The differences between the observed percentages and the corresponding standard values are given in special columns, ivith their averages. *
NO.
.SEX
AGE IN
D.\ys
BRAIN WEIGHT
PERCENTAGE OF WATER
BRAIN OBSERVED
PERCENTAGE OF
WATER
STANDARD FOR THE
PERCENTAGE OP
WATER
STANDARD FOR THE
Same age
Difference in observed
Same brain weight
Difference in observed
grams
H a
f
13
0.880
86.39
85.^0
+0.99
86.82
-0.43
b
f
17
1.024
84.15
83.82
+0.33
85.08
-0.93
c
f
23
1 . 135
82.00
81.93
+0.07
83.21
-1.21
d
f
28
1.166
80.83
80.74
+0.09
82.70
-1.87
e
m
32
1.215
80.31
80.04
+0.27
81.70
-1.39
f
f
37
1.101
80.12
79.55
+0.57
83.78
-3.66
g
m
43
1.295
80.24
79.32
+0.92
80.56
-0.32
Averag
e
+0.48
-1.40
that the underfed brain is shghtly underdeveloped for its age, but somewhat overdeveloped for its weight. Similar relations have been revealed by the comparisons already made. Normally about 0,5 per cent excess in percentage of water in the brain would mean at the early ages approximately one or two days' retardation in development (compare table 74 in 'The Rat/ Donaldson, '15).
From the same litter (Litter H) I took with each of the above individuals a second rat for the study of the myelination, because it is known that the percentage of water in the brain is correlated with its myelination. The brains under seventeen days of age showed no fibers in the frontal sections, as stained with PalKultschitzky method. The twenty-eight-day brain showed only a few faintly stained fibers in the cortex, the fibers in the corona radiata (designated C. E. by Watson, '03) being already myelinated. Material above thirty-seven days was not examined. This passing examination of a small number of cases roughly indicates, therefore, that the first appearance of myelina
220 NAOKI SUGITA
tion in somewhat retarded, because, according to the investigation of Watson ('03), myelination in the corona radiata should have begun at eleven days and radiations into the cortex should have been recognized at twenty-four days. But a more detailed test for this j5rocess is required before any special use can be made of the results.
14. RELATIVE QUANTITIES OF THE ALCOHOL EXTRACTIVES
In my former paper (Sugita, '17 a) a chart, based on the data given in 'The Rat' (Donaldson, '15), was presented to show the absolute quantity of sohds contained in the Albino brain according to the brain weight. For comparison with this, I calculated also the relative quantity of alcohol-extractive substances in the Albino brains, as shown by comparing the initial weight of the brain with its weight after extraction by 80 per cent alcohol (for twenty-four hours) and 90 per cent alcohol (for twenty-four hours) according to a uniform procedure. As the brains were treated uniformly throughout the investigation, the results are comparable among themselves.
The results from 120 normal albino rat brains, grouped in twenty brain-weight groups (Groups I to XX), are given here in table 15 and plotted also in chart 1, in which the smooth curve (in a dotted line) represents the percentage weight of the extracted brain on the fresh brain weight. In chart 1, the graph which presents the absolute amounts of solids (in grams) according to the brain weight is also given in a solid line based on the chart in my former paper (chart 12, Sugita, '17 a). It was remarked previously (Sugita, '17 a) that in the Albino brains weighing between 0.95 gram and 1.4 grams, that is, between ten and thirty-five days of age, the rate of increase in solids is somewhat higher than in the periods before and after that phase, and this fact was formerly interpreted as indicating that, during this phase, the myelination in the brain had been proceeding very actively. This interpretation is now supported by the graph which gives the percentage weight of the brain. This graph varies inversely to the amount of the alcohol-extractives
GROWTH OF THE CEREBRAL CORTEX
221
and, as it decreases relatively rapidly in the phase during which the brain grows in weight from 0.9 gram to 1.35 grams, or in the ages between nine and thirty-three days, it shows that during that phase the alcohol-extractives increased.
The turning points in the both graphs marked with crosses X and XX) and asterisks (* and **), respectively, are in fair
•/n
"•r
500
78
!.
"■■—
-...
y
400
74 72
--.'.._
. ~
c
>
^
y
^v
\
^
'^
iou
68 66 64 62 60
1
/
/-'
i'i"
•
200
!
/
•
1
^
^
)00
-^
^
-^^
i
Q2 0.3
0.5 Q6 QT
09 10 \\ i.2 13 1.4 1.5 1.6 1.7 1.8 19 2.0 W
Chart 1 The dotted line shows the ratio between the initial brain weight and the weight after its dehydration and extraction in 80 per cent alcohol (for twentyfour hours) and 90 per cent alcohol (for twenty-four hours) according to a uniform procedure, plotted on the brain weight. The data were taken from table 15. The graph was drawn connecting the middle points of each pair of entries, and ** indicate the turning points in the graph.
The solid line shows the absolute weight of the solids in the brain according to the brain weight. The data were taken from table 74 in 'The Rat' (Donaldson, '15) and calculated by me. * and ** indicate the turning points in the graph.
For the ratios of brain weight the scale is given on the left side of the chart and for the absolute weight of the solids the scale is given on the right side.
coincidence, so that it may be concluded that the mass of the alcohol-extractives would be in proportion to the grade of myelination in the brain, and by following the former the progress in myelination could be estimated roughly.
It must be emphatically stated that my figures given in table 15 do not represent the total quantity of the alcohol-extractives,
222
NAOKI SUGITA
TABLE 15
Giving for each brain-iveight group of the normal albino rat the average initial brain-weight in the fresh condition and the brain weight after dehydration and extraction in 80 per cent alcohol (for twenty-four hours) and 90 per cent (for twentyfour hours) by a uniform procedure. The ratio of the final brain weight to the ^initial weight is given in the last column as a percentage value. Based on observations on 120 albino rats, sexes combined.
BRAIN WEIGHT
BRAIN-WEIGHT GROUP
NUMBER OF CASES
BRAIN WEIGHT WHEN FRESH
AFTER
DEHYDRATION IN
80 AND 90
PER CENT ALCOHOL
RATIO TO THE
INITIAL BRAIN WEIGHT
gravis
grams
per cent
II (birth)
6
0.271
0.213
78.6
III
8
0.343
0.267
77.8
IV
9
0.428
0.332
77.5
V
14
0.543
0.416
76.7
VI
5
0.636
0.479
75.4
VII
4
0.755
0.571
75.7
VIII
10
0.844
0.630
74.7
IX (10 days)
5
0.954
0.714
74.8
X
6
1.047
0.757
72.3
XI (20 days)
5
1.161
0.820
70.6
XII
5
1.245
0.874
70.2
XIII
8
1.341
0.921
68.6
XIV
5
1.449
0.989
68.2
XV
7
1.558
1.074
68.9
XVI
8
1.667
1.131
67.9
XVII
6
1.721
1.170
68.0
XVIII (90 days)
5
1.832
1 222
66.7
XIX
1
1.924
1.317
68.4
XX
3
2.037
1.369
67.2
because the extraction was not complete. My figures are only by-products in a study on histological technique, and to obtain the total quantity of the extractives the brain must have stayed much longer in alcohol of a higher concentration. My data therefore give merely the relative values for the quantity of the alcohol-extractives, but are comparable among themselves and with the values from the underfed brains treated in the same manner.
In giving the ratio of the brain weight after extraction in alcohol (by this method) to its initial weight, no correction was made for the weight of water replaced by alcohol, because my object was
GROWTH OF THE CEREBRAL CORTEX 223
only to compare the results among themselves and not to determined the exact quantity of the extractive substances.
Table 16 gives for each group in this study the ratio of the brain weight after dehydration in 80 per cent alcohol (for twentyfour hours) and in 90 per cent alcohol (for twenty-four hours) to its initial weight in the fresh condition, calculated in the same way as in table 15 and each paired with the standard ratio for the same age, quoted from table 15. Thus compared, the underfed brains show in general a higher ratio, the difference amounts to 1.0-4.3 per cent, on the average 1.9 per cent, while the difference in the control brains is generally low, on the average + 0.4 per cent.
This examination tells us roughly that in the underfed brains the alcohol-extractives are somewhat less in quantity than in the normal brain, if the age be taken as the standard of comparison, and, therefore, it may be concluded that they are somewhat retarded in the formation of alcohol-extractive substances and therefore in myelination. Reviewing tables 14 and 16 together, we see that during underfeeding the myelination process or the increase in the alcohol-extractives is retarded slightly, but is going on, not greatly affected by the outside influence, regularly according to its age. It is fair to say, however, that the differences thus determined by extraction are seemingly less than those shown by the histological tests,
15. A DISCUSSION OX THE RELATION BETWEEN THE BODY
WEIGHT AND THE BRAIN WEIGHT IN THE UNDERFED
ALBINO RATS
By examining table 4 it will be readily seen that under severe underfeeding at an early age, the increase in the body weight and the brain weight, according to the age, is notably reduced, and, as a consequence, the acutely underfed (Series I, chapter 5 and table 1) have lost, in the course of first twenty days after birth (during suckling period), about 29 per cent in body weight, but only 8 per cent in brain weight, when compared with the corresponding standard values for the same age. By chronic starvation, during which the young (excessive in number) were left
224
NAOKI SUGITA
TABLE 16
Giving for each litter group in this study the average age, the initial brain weight in the fresh condition and the brain weight after extraction in 80 per cent alcohol {for twenty-four hours) and 90 per cent alcohol {for twenty-four hours) by a uniform procedure, and the ratio of the latter to the initial weight. The corresponding standard values for the same age loere calculated 07i the basis of the data in table 15 and compared with each arid the difference between them given as an average for each group. This table %uas condensed from table 16a {unpublished) for individual cases. The averages for the test andcontrol groups are given at the end of the table.
SERIES, LITTER AND
TEST CONTROL
AVERAGE AGE
AVERAGE BRAIN WEIGHT
AFTER EXTRACTION IN 80 PER CENT AND 90 PER CENT , ALCOHOL
standard ratio for the brain
of the same age
DIFFERENCE
GROUP
Final brain weight
Ratio to
the initial
brain
weight
FROM THE STANDARD
Series I
A c, a, d, f
b
b, g
i
T. I T. II
C. I C. II
days
715
817
gram.1
0.584 1.024
0.688 1.278
grams
0.450 0.779
0.517 0.928
per cent
77.2 76.0
75.7 72.7
per cent
75.7 72.8
75. li. 72.3
per cent
+ 1.5 +3.2
+0.3 +0.4
Series I
B a, c, e, f
i
b, d
T. I T. II
C. I C. II
919
6 18
0.644 1.052
0.543 1.144
0.488 0.799
0.414 0.826
76.1 76.0
76.4
72.2
74.9 71.7
76.1 72.1
+ 1.2 +4.3
+0.3 +0.1
Series I
C a, c, d
b, e
T. II C. II
20 22
1.105 1.307
0.816 0.934
73.9 71.5
72.9 71.8
+ 1.0 -0.3
Series I
D a, c, d
e
b f
T. I T. II
C. I C. II
1218
9 22
0.778 1.089
0.870 1.220
0.584 0.795
0.656 0.863
75.1 73.0
75.4 70.8
73.7 72.0
74.5 71.0
+ 1.4 + 1.0
+0.9 +0.2
Series I
Ea, b, c, d
e
T. I C. II
1213
0.835 1.024
0.626 0.760
75.0 74.1
73.7 73.4
+ 1.3 +0.7
Series II
F a, b
c-k
T. I T. II
13 25+
0.832 1.198
0.636 0.862
76.7 72.3
73.4 70.7
+3.3 + 1.6
GROWTH OF THE CEREBRAL CORTEX
225
TABLE IQ— Continued
SERIES, LITTER AND GROUP
TEST CONTROL
AVERAGE AGE
AVERAGE BRAIN WEIGHT
.AFTER EXTRACTON
IN 80 PER CENT AND
90 PER CENT
ALCOHOL
■n.- , Ratio to hr«i. the initial
Standard ratio for the brain
of the same age
DIFFERENCE FROM THE STANDARD
Series III
Ga-g
h-j
T. I T. II
days
11+
22
gra m s
0.844 . 1.154
gratnts
0.641 0.833
per cent
76.0
72.2
per cent
73.9
71.2
per cent
+2.1 + 1.0
Average \ (Ser. I-III)/
Average 1 (Ser. I) j
T. I T. II
C. I C. II
11+
20+
818+
0.753 1.104
0.700 1.195
0.571 0.814
0.529 0.862
76.0 73.9
75.8 72.3
74.2 71.9
75.3
72.1
+ 1.8 +2.0
+0.5 +0.2
continuously with the mothers (Series II and III, chapter 2 and table 2), the loss in the brain weight is relatively less, in some individual cases nothing, while the body weight suffers much more, compared with the acutely underfed groups (Series I).
The observed body weight and the brain weight of each individual in this study are plotted separately for each litter in chart 2, A to H, according to the advancing age. Comparing the set of graphs both for the body weight and the brain weight within every litter, it is clearly seen at a glance that the courses of the graphs are similar, so that one, which advanced in age but has a smaller body weight, has also a relatively smaller brain weight, and vice versa. From this it is concluded that, though the brain, with a strong impulse to grow, regularly increases in weight with age and is only slightly affected by outside influence, yet it is controlled somewhat by the growth in the entire body. Thus, within certain limits, the brain weight may be said to be a function of the body weight: a rat reduced in body weight by starvation has a brain also reduced in weight and, on the other hand, a rat excessive in body weight for its age, through overfeeding, has an exces'S of brain weight for its age, as seen in the control groups shown in table 4. In the interrupted starvation tests (Series I), an average reduction of 29 per cent in the body weight
THE JOURNAL OF COMPARATIVE NEUROLOGY, VOL. 29. NO. 3
226
NAOKI SUGITA
yns, yni
"-^
JTli
«
,--y
^
-"
15 20 25 <J.
10 15 20 25 30 35 #0 ic^t
Chart 2 Giving for each litter in this study the relation between the body weight and the brain weight of the individuals. The capital letters for each small chart designate the litter. The data given in table 3 were plotted according to the advancing age in days. • ■ ' '— '• Observed body weight of the underfed, in grams. %
o o Observed brain weight of the underfed, in grams.
Observed body weight of the controls, in grams.
Observed brain weight of the controls, in grams.
For the body weight the scale is given on the left side and for the brain weight the scale is given on the right side of the chart.
GROWTH OF THE CEREBRAL CORTEX 227
is accompanied by 8 per cent reduction in the brain weight in the test rats, and an excess of 14 per cent in the body weight by an excess of 6 per cent in the brain weight in the controls. These relations indicate that the brain weight is affected in abnormal conditions of nutrition during early life so that its percentage is altered by about one-third the percentage of the change of the body weight, either plus or minus, as compared with the standard values. On the other hand, in chronic inanition (Series II and III) where the young rat is not disturbed, the brain-weight loss was also 8 per cent against a body weight loss of 39 per cent. It appears, therefore, that during the early helpless period the brain development is highly disturbed by the changes in the environmental conditions represented by removal from the nest, but that when the rats are not disturbed it is much less affected even by severe underfeeding.
Table 17 gives for each group in this study the brain weight — body weight ratio, in percentage value, paired with the ratio obtained from the corresponding standard values for the same age and sex, calculated on the data given in table 4. The complete data for each individual are contained in table 17 a (unpublished) from which table 17 was condensed. In the underfed the above ratios are all higher than the standard, as was to be expected, while in the controls lower ratios are sometimes seen, which, in turn, means an overgrowth of the body. The average differences for each litter and group are given and the values are indicative of the severity of starvation combined with the special characteristics of the litter. Within each litter the range of the differences is narrow but the evidence for this statement is furnished by the unpublished detailed table 17 a.
16. A DISCUSSION ON THE CHANGE IN SHAPE OF THE CEREBRUM
In my first paper (Sugita, '17) it was stated that the Albino cerebrum becomes relatively longer as the age advances. During starvation, the rate of increase in every dimension diminishes considerably, but the relations between the three dimensions remains nearly unchanged, so that, as a result, the underfed brain is somewhat elongated in shape in comparison with the standard
TABLE 17 Giving for each litter group in this study the average age, the sex, th
brain weight —
body weight ratio, compared with the same ratio for the standard rat of the same age and sex. The difference of the ratio for each group is given in the last column This table was condensed from table 17a (unpublished) for the indiAt the foot of the table the averages for the test and control groups
of the table, vidual cases are given.
SERIES, LITTER AND GROUP
TEST CONTROL
AVERAGE AGE
SEX
RATIO OF
BRAIN
WEIGHT TO
BODY
WEIGHT
The same
in standard
rat of the
savie age
DIFFERENCE FROM THE STANDARD
days
per cent
per cent
per cent
Series I
A c, a, d, f
T. I
7 —
1 m, 3 f
7.9
6.5
+ 1.4
h
T. II
15
a f
7.4
6.3
+ 1.1
b, e, g
C. I
8
3 m
6.4
6.8
-0.4
i
C. II
17
1 f
4.2
6.1
-1.9
Series I
B a, c, e, f
T. I
9
3 m, 1 f
8.7
6.7
+2.0
i
T. II
19
1 m
8.3
6.0
+2.3
b, d
C. I
6
2 f
7.6
6.5
+ 1.1
g, h, J
C. II
18
3 f
5.7
6.0
-0.3
Series I
C a, c, d
T. II
20
2 m, 1 f
7.7
5.8
+ 1.9
b, e
C. II
22
2f
5.3
5.6
-0.2
Series I
D a, c, d
T. I
12
1 m, 2 f
11.3
6.8
+4.5
e
T. II
18
1 m
8.4
6.2
+2.2
b
C. I
9
1 m
7.8
7.1
+0.7
f
C. II
22
1 m
5.1
5.6
-0.5
Series I
E a, b, c, d
T. I
12
3 m, 1 f
8.6
6.8
+ 1.8
g, h
T. II
20
2f
7,0
5.6
+ 1.4
e, f
C. II
17
Im, 1 f
5.6
6.4
-0.8
Series II
F a, b
T. I
13
1 m, 1 f
9.1
6.8
+2.3
c-1
T. II
25+
4 m, 6 f
7.5
5.1
+2.4
Series III
Ga-g
T. I
11 +
4 m, 3 f
10.3
6.9
+3.4
h-j
T. II
22
2 m, 1 f
9.3
5.5
+3.8
Average 1
T. I
11
9.3
6.8
+2.5
(Ser. I-III)/
T. II
21 +
7.9
5.8
+2.1
Average 1
C. I
8
7.3
6.8
+ 0.5
(Ser. I) /
C. II
19+
5.2
5.9
-0.7
228
GROWTH OF THE CEREBRAL CORTEX 229
brain, which is the same in weight but younger. As shown in table 5, in the underfed brains the measurement L.G (the sagittal diameter) is on the average nearly 2 per cent (about 0.25 mm. in a brain weighing 1.0 gram) greater. than the standard, while, on the other hand, as shown in table 6 a (unpublished), in the underfed the cortical thickness at the frontal pole (locality I) .which was measured almost in the same direction w^ith L.G is also greater by 10 per cent (about 0.25 mm. in a brain weighing 1.0 gram) than the standard for the same brain weight, while the cortex at the occipital pole (locality V) is nearly equal to the standard in thickness. Considering together the above facts, the sagittal length of the central nuclei only, if measured between the frontal and occipital poles, would be supposedly about the same in both the underfed and the standard brains weighing alike. On the other hand, the width W .B is, in the underfed, less by nearly 2 per cent (about 0.3 mm. for 1.0 gram brain) than in the standard, and the cortical thickness at locality VII, which was measured at the side of the cerebrum, is thicker in the underfed by nearly 10 per cent (about 0.4 mm. for the both hemispheres in a 1.0 gram brain (based on the unpublished table 6 b for each locality) , and therefore the central nuclei in the underfed are less in width by about 0.7 mm. (for a 1.0 gram brain) than the standard for the same brain weight. In short the central nuclei are notably elongated in shape in the underfed brain compared with the normal brain of like weight.
17. A DISCUSSION ON THE THICKNESS OF THE CORTEX IN THE
UNDERFED
As described in Chapter 7, the cortical thickness in the starved brain is on the average markedly greater than the standard for the same brain weight. In the sagittal sections, the locality I surpasses the standard most, the localities II and III are the next, while the localities IV and V are almost equal in thickness to the standard (these statements are based on the unpublished table 6 a for each locality). This order in which the localities surpass the standard in thickness is the same as the order in rate of increase in the cortical thickness during the post
230 NAOKI SUGITA
natal growth (Sugita, '17 a). The same statement is true for the iocahties VI, VII, and VIII in the frontal sections (based on the unpublished table 6 b). The order in the rate of increase in the cortical thickness is an index of the grade of intensity in cell migration to those localities and of the growth impulse of the elements there. From previous studies (Sugita, '17 a), it was found that, as a rule, the cortical thickness decreases from the frontal to the occipital pole and from the dorsal to the ventral aspect, and the nearer a locality is to the ventricular wall or the matrix the more rapid the rate of increase in the thickness of the cortex. In underfed brains, the localities which show normally the higher rate of increase in thickness are also greater in the cortical thickness when compared with the standard. So, in the underfed, the cerebral cortex is generally thicker than the standard for the same brain weight and thicker in each locality in proportion to the rate of increase in the thickness of that locality under normal conditions.
In short, the growth in the cortical thickness in the case of the underfed is more advanced than that of the normall brain of the same weight, which is, of course, younger.
18. A DISCUSSION ON THE RELATION BETWEEN CELL DENSITY AND THE COMPUTED VOLUME OF THE CEREBRAL CORTEX
As stated earlier, the cell density of the cerebral cortex, represented by the number of nerve cells in two unit volumes (N), is, in the underfed Albino brain, under sixteen days in age, considerably higher than the standard for the same age, and accordingly the cell size in the underfed must be smaller than the standard size and, by inference, the cell attachments also underdeveloped for the age. The relations between these data will be examined now according to my measurements as presented in this paper.
The cortical area as measured in the sections from the underfed brains proves to be slightly greater than the standard values for the same brain weight, but on the other hand, it is distinctly less in brains under sixteen days of age than the standard values
GROWTH OF THE CEREBRAL CORTEX 231
for the same age, which belong to brain weights higher by about 10 per cent.
Let us take as an example an underfed brain which weighs less than 1.0 gram for examination. The computed volume of the cerebral cortex is in the underfed smaller on the average by 16 per cent than the standard for the same age (chapter 9). As shown by calculation, the computed number of nerve cells in the entire cortex is almost the same in both the standard and the underfed, throughout all ages, so that the process of cell division appears to have been going on undisturbed by the condition of underfeeding. The cell density, the cell size, and the cortical volume must therefore be regulated so as to provide the cerebral cortex with the number of cells fixed according to the age, regardless of the starvation.
To present the relation, the formula A^ X L.F X W.D X T was used. The value. of iV X L.F X W.D X T has proved in my present material fro*n the underfed to have been 1,7 per cent higher than the standard, but as this is open to some correction, it may be regarded as approximately the same in both the underfed and the corresponding standard. To be less in the cortical volume, which was computed by the formula L.F X W.D X T, by about 16 per cent or more, the cell density must be increased by about 19 per cent or less theoretically. * This latter figure is fairly in accord with that obtained in my direct observation; that is, 17 per cent excess in the number of cells in a unit volume in the underfed brains (chapter 10). To be reduced in cortical volume by 16 per cent or more, the individual cell must theoretically be reduced in volume also in the same ratio, in order not to be reduced in total number. My results in cell-size measurement showed that the individual cells measured are reduced in average diameter by about 12 per cent, and accordingly in average volume by about 30 per cent or more. These figures appear somewhat higher than was to be expected, but it must be recalled that these figures apply only to the largest cells found in the measured locality, and this class of cells may suffer a disproportionate arrest, so that the figures do not indicate what has" taken place in the small cells and those of average size. Furthermore, in the
232 NAOKI SUGITA
cerebral cortex the neuroglia, the intercellular tissue and the blood-vessels occupy considerable space and these may not be reduced in volume in the same proportion as the large nerve cells. These facts combined seem to furnish an explanation why the largest nerve cells, which have been here studied, deviate somewhat in size from the figures theoretically to be expected.
The data here presented show, I think, that the relations betv/een the cell density and the cortical volume in the underfed fit with the formulas presented earlier and which represent the relations in the normal Albino brains.
19. A DISCUSSION ON THE PROCESS OF MYELIN ATION
Tables 14 and 16 supply the data on which the myelination process in the underfed Albino brain may be tentatively discussed.
In Donaldson's series ('11), which consisted of twenty-two litters of albino rats in which the underfeeding was begun at 30 days of age and in which all were killed after three weeks and compared with the controls from the same litter, the average brain weight of the underfed was 1 .402 grams and the percentage of water 79.28, while the average brain weight of the controls was 1.519 grams and the percentage of water 79.39. Here the underfed had 0.11 per cent less water. By examining the sections from the underfed and the controls, the author could not discover any recognizable difference in myelination between them. Hatai ('04) made a partial starvation experiment, extending over three weeks, using the albino rats in the growing stage, about thirty days old. In this series, the final average brain weight was 1.341 grams and the percentage of water 79.15 or 0.21 per cent less than in the controls from the same litter and killed at the same age and in which the final brain weight was 1.508 grams and the percentage of water 79.36. In the same series, the solids extracted with alcohol and ether were determined. The average amount c f the extractives in the test brains was 46.7 per cent, or 0.9 per cent more than in the controls, in which it was 45.8 per cent. Though higher in percentage in the underfed.
GROWTH OF THE CEREBRAL CORTEX . 233
the absolute mass of the extractive substances is 0.065 gram (about 5 per cent of the brain weight) less than in the controls of the same age. The absolute weights were in the underfed 0.626 gram and in the controls 0.691 gram. These extractives represent mainly the myelin which is contained in the sheaths of the nerve fibers, and the above results mean that the extractive substances are increasing at the same rate or slightly slower in the underfed than in the controls.
In my material as seen in table 14, the underfed brains contain slightly more water (by 0.48 per cent on the average) than the standard of like age, and, as presented above (chapter 13), the frontal section showed a higher percentage in area of the cortex against the area of the central nuclei, which latter contain the bulk of the mj'elin sheaths. On the other hand, the underfed brains contain less water (by 1.4 per cent on the average) than the standards of the same brain weight. Comparisons of the absolute weight of the solids in the underfed brain with the corresponding standard value for the same brain weight and for the same age, based on data in 'The Rat' (Donaldson, '15), are given in table 18. The underfed has shown as a rule considerably less in total solids than the standard for the same age, though it proved to be only slightly higher in percentage of water than the standard (also table 14). ■,
From the above, the absolute mass of the solids in the underfed brain seems to be more than in the standard for the same brain weight, but less than in the standard for the same age. So the increase in solid mass is somewhat retarded by starvation. It will be noted that in my series of rats the percentage of >vater in the underfed was 0.48 per cent above that in the standards of like age and this is the reverse of the results reported by Donaldson and by Hatai in the studies just cited. This discrepancy probably depends on the fact that my rats are absolutely much younger than those studied by the other authors, but the explanation must await further study.
Since, as shown in chart 1, the relative values of the quantity of the alcohol-extractives has a fixed relation to the absolute weight of the sohds in the brain, the above statement may be also
234
NAOKI SUGITA
TABLE 18
Giving for each individual in Litter H {Series II) the sex, the age, the observed brain weight, percentage of water, and the calculated absolute weight of the solids in the brain, compared with the standards for the percentage of water and the mass of solids for the brains of the same weight and of the same age. Averages are given in the last line.
STARVED
STANDARD
Sex
Age
Brain weight
Percentage of water
Mass of solids
For the same brain weight
For the same age
No.
Percentage of water
Mass of solids
Brain weight
Percentage of water
Mass of solids
H a b c d e f g
f
f
f
f
m
f
m
13 17 23 28 32 37 43
grams
0.880 1.024 1.135 1.166 1.215 1.101 1.295
per cent
86.39 84.15 82.00 80.83 80.31 80.12 80.24
grams
0.120 0.162 0.204 0.224 0.239 0.219 0.256
per cent
87.45 85.08 83.21 82.60 81.70 83.78 80.51
grams
0.110 0.153 0.191 0.203 0.222 0.179 0.252
0.187
grams
1.003 1.099 1.208 1.282 1.338 1.391 1.468
per cent
85.40 83.82 81.93 80.74 80.04 79.55 79.32
grams
0.146 0.178 0.218 0.247 0.267 0.285 0.304
Average
28
1.117
82.01
0.203
83.48
1.256
81.54
0.235
confirmed by the data given in table 16, in which it is clearly shown that in the underfed the alcohol-extractives are slightly less developed as compared with the standards for the same age.
20. SUMMARY
1. Young albino rats were experimentally starved throughout the suckling period, by one of the following methods :
Series I. Separation of the young from the nursing mother for the maximum time each day.
Series II. Entrusting one mother with an excessive number of young (over seventeen) at the same time and thus reducing the amount of milk for each young one.
Series III. Starving the nursing mother and thus reducing the quantity of milk secreted.
I employed five litters for Series I, two litters for Series II, and one litter for Series III; in all forty-six individuals were subjected to experiment and there were fourteen controls.
GROWTH OF THE CEREBRAL CORTEX 235
2. The underfed and the controls were killed at different ages (between three and forty days) and the body measurements and the brain weights recorded. The brain was fixed, sectioned, stained, and examined according to the standard procedure previously adopted for these studies (Sugita, '17, '17 a, '18 b, '18 c) and the size of the cerebrum, the thickness of the cerebral cortex, the area of the cortex in the sections, the number of nerve cells in a unit volume of the cortex, and the size of the pyramidal and the ganglion cells, were all determined and then corrected to the values for the fresh condition of the material, by the use of the correction-coefficients devised for these purposes.
Using these data, the relative volume of the cerebral cortex and the number of nerve cells in the entire cerebral cortex were computed, employing the formulas already devised by me (Sugita, '18 b). All the observed and computed data were compared with the corresponding respective standard values for the normal Albino brain of the same weight or of the same age, as given in my previous papers (tables 3, 4, 5, 6, 8, 11 and 13).
3. In Series I the underfed rats were found to be 29 per cent less in the body weight and 8 per cent less in the brain weight, than the standards for the same ages (between three and forty days). In Series II and III the underfed rats were 39 per cent less in the body weight while 8 per cent less in the brain weight. It appears from this that starvation without removal from the nest, and the corresponding disturbance to the young, retards the growth of the brain relatively less, despite the greater arrest in the body growth.
The underfed brain weight was found on the average 24 per cent higher than the standard for the same body weight. The brain weights in the underfed have values between the standards for the same age and those for the same body weight, but generally fall nearer to the former.
The brain weight is a function of the body weight : a rat which is more reduced in body weight by starvation has a more reduced brain weight. The brain weight — body weight ratio is always higher in the underfed than in the standard for the same age, and the difference between the ratios roughly indicates the severity of
236 NAOKI SUGITA
the starvation. Thus in those severely underfed the difference is higher than in those less severely underfed.
4. The shape of the cerebrum in the underfed is slightly elongated as compared with that of the standard with the same brain weight and approximates that for the same age. As the result of underfeeding, the growth of the central nuclei seems to be more arrested in width than in length and the changes in the growth in the cortex in thickness matter little for the shape of the cerebrum.
5. The thickness of the cortex is on the average 10 per cent greater in the underfed in the localities I, II, VI, and VII than in the standards for the same brain weight. By averaging according to the entire section, the average thickness in the sagittal section of the underfed exceeds that of the standard by 5.3 per cent and in the frontal section by 8.7 per cent. The general average thickness of the cortex in the underfed is consequently greater by about 7 per cent than the standard for the brain of the same w^eight. The locahties which normally show the higher rate of increase in thickness during the postnatal growth are those which are notably greater in the cortical thickness in the underfed brains.
6. The relative volume of the cerebral cortex, computed by the formula L.F X W .D X T, is generally smaller in the underfed than in the standard for the same age. In the underfed brains weighing up to 1.0 gram (that is, under sixteen days of age), it is on the average less by 16 per cent or more, while in the underfed brains weighing more than 1.0 gram it is 6 per cent greater than the standard. So it may be said that, in rats underfed severely, the cortical volume is considerably retarded in growth in early period of development, but this is somewhat compensated or overcompensated later when the brains attain the weight of more than 1.0 gram or in age of more than sixteen days.
7. The cell density in the cerebral cortex, represented by the sum of the number of pyramids in the lamina pyramidahs and the number of nerve cells in the lamina ganglionaris in two unit volumes of 0.001 mm.^, is considerably higher in the underfed than in the standard rat for the same age. The excess in cell
GROWTH OF THE CEREBRAL CORTEX 237
density in underfed brains weighing less than 1.0 gram is on the average 17 per cent, and that in underfed brains weighing more than 1.0 gram is almost equal to the standard for the same age. As in the underfed brains weighing less than 1,0 gram, the relative volume of the cortex is smaller than in the standard, it follows that the underfed brains, if they contain the same number of cells, must have a relatively higher cell density in a unit volume to balance the smaller total volume of the cortex.
8. The relative value of the computed number of the nerve cells in the entire cortex, calculated by the formula A^ X L.F X W.D X T, in the underfed was compared with the corresponding standard value for the same age and the former was found to be only slightly higher than the latter, so that they may be regarded as practically the same. If so, the process of the cell division in the cerebrum must have progressed according to the advancing age, in spite of the starvation.
9. The size of the nerve cells was studied on the pyramids in the lamina pyramidalis and on the ganglion cells in the lamina ganglionaris. The cell body of the pyramids in the underfed brains weighing less than 1.0 gram is smaller by 11.2 per cent in average diameter and that in brains weighing more than 1.0 gram smaller by 8.3 per cent than the standards for the same age. The corresponding figures for the nuclei of the pj^ramids are 15.3 per cent and 11.0 per cent.
The cell body of the ganglion cells in the underfed brains weighing less than 1.0 gram is smaller in average diameter by 11.8 per cent, and that in the underfed brains weighing more than 1.0 gram is smaller by 3.1 per cent than the standards for the same age. The corresponding values for the nuclei of the ganglion cells are less by 12.5 per cent and 5.1 per cent, respectively. So, on the average, the nerve cells in the cortex of the underfed of all weights are smaller in average diameter by about 9 per cent (for the underfed brains weighing less than 1.0 gram by about 12 per cent and for those weighing more than 1.0 gram only by about 6 per cent), and consequently smaller in volume by about 25 per cent than the standard cells of the same age. These determinations apply only to the largest cells found at the measured locality.
10. The underfed brains (Series II) contain on the average sUghtly (0.48 per cent) more water, if compared with the normal brain of the same age, and somewhat (1.4 per cent) less water, if compared with the normal brain of the same weight. This means probably that, in terms of the percentage of water, the underfed brain is slightly underdeveloped for its age and somewhat overdeveloped for its weight. If the absolute weight of the soHd mass be calculated and compared with the standard for the same brain weight and sex, the solids are found to be somewhat more in the underfed and if the same compared with the standard for the same age and sex the solids are always less in the underfed. The relative value of the alcohol-extractives, obtained by comparing the initial brain weight with its weight after dehydration and extraction in 80 per cent alcohol (for twenty-four hours) and 90 per cent alcohol (for twenty-four hours) according to a uniform procedure, shows that in the underfed brains the amount of the alcohol-extractives is somewhat smaller than in the normal of the same age.
The above observations indicate that in thie underfed the myelination process in the brain is somewhat retarded for the age. This assumption was supported in a general way by the direct examination on the sections obtained from the underfed brains.
11. Briefly, we conclude that by starvation in the early days the brain suffers much in its development in toto, but the cell division is going on quite normally according to its age. The growth of the cells in size is retarded and the formation of myelinated fibers somewhat diminished by inanition. So the smaller weight and size of the underfed brain is due to an arrest in the growth and development of the constituent neurons and not to a decrease in their number.
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