Paper - Quantitative chemical changes in the human brain during growth (1919)

From Embryology

MacArthur CG. and Doisy EA. Quantitative chemical changes in the human brain during growth. (1919) J Comp. Neurol. 30: 445-.

Quantitative Chemical Changes In The Human Brain During Growth

C. G. MacArthur, and E. A. Doisy

The Biochemical Laboratory of the University of Illinois, and Stanford Medical School

Three Charts

It seemed desirable to develop a more complete growth series of quantitative determinations of the important constituents in the human brain than has heretofore been published (KochMann, '07- '08). During fetal life and infancy these changes are most interesting, but least studied. The chemical differentiation during growth in young pigs (Koch, '13) and young rats (W. and M. L. Koch, '13) has received attention, but early human life has been curiously neglected.

Method of Analysis

The method of analysis is essentially the same as that used by others in quantitative brain work.^ The outline on page 446 gives the main points.

Limitations and Errors

It needs to be kept in mind that disease caused the death of the people whose brains were analyzed. Though the brain in no case showed appreciable lesions, yet it is always possible that chemical alterations might have taken place before death.

Only one brain (except in the case of the three-month fetal brains) was analyzed for each of the ages given. Of course there is no guarantee that each was an average brain. Moreover, we have, because of the few analyses, no means of finding out the average deviation. Not until many such series have been developed shall we be able to state what normal brain growth really is. To a certain extent, a smooth curve averages the data, but this may introduce larger errors than it attempts to average. There is no way of knowing definitely that a curve should be regular as given or made up of a series of waves of different sizes. This also can be determined only by a larger number of investigations.


  • For detail of method and formulae for calculation of results see Koch, W., J. Am. Chem. Soc, 31, 1329, ff. 1909; Koch, M. L., and Voegtlin, C, Hyg. Lab. Bull. No. 103, p. 67. 1916.


Moist brain tissue


Add alcohol and extract alternately with alcohol and ether

EXTRACT^ (fractions 1 AND 2)


RESIDUE (fractions 3 AND 4)


Evaporate to dryness, emulsify with water, precipitate with CHCI3 in 0.5 per cent HCI solution


Dry, weigh, and extract with hot water.


Precipitate (fract.l): (Colloidal)


Filtrate (fract 2): (Crystalloidal)


Filtrate (fract 3) : (Crystalloidal)


Residue (fract. 4): (Colloidal)


Lipoids


Organic constitu

Inorganic constit

Proteins


Phosphatids


ents:


uents :


Nucleoprotein (a)


Cerebrosides


Hypoxanthin


Ammonium


Nucleoprotein (b)


Sulphatids


Tyrosin


Iron


Neurokeratin


(Cholesterol, etc.)


Leucin


Sodium


Urea


Potassium


Inosit


Calcium


Taurin


Magnesium


Peptones


Chlorides


Sarcolactic acid


Inorganic constituents (see fract. 3)

Organic constituents (see fract. 2)

Lipoid sulphur


Neutral sulphur


Inorganic sulphur


Protein sulphur

(Sulfates)


Lipoid phosphorus


Organic extractives


Inorganic phosphorus (Phosphates)

Protein phosphorus


Phosphorus

Lipoid nitrogen


Organic nitrogen


Inorganic nitrogen


Protein nitrogen


2 Substances in italics were determined in this investigation.



If the thirty-five-year-old brain is normal, there is a rather wide range of variability. It will be noticed that the total solids in this brain are 5 per cent higher than in the other adult brains. This cannot be an analytical error, because the same amount was obtained in two analyses made at different times in the series.

The brain marked '8-24 mo.' was labeled '2 years' when sent for analysis. There seems to be no good reason for questioning the accuracy of this information. However, the weight of the brain indicates an infant of a few months. Its water content suggests an infant of about eight months, while some of the phosphatids would favor a slightly greater age, as would the weight of cerebellum and stem. Very likely this brain was two years old, but subnormal. In spite of the uncertainty concerning the brain, it is included in this series because it was the only one of this age available, but it is considered with the greatest reservation in forming general conclusions.

No brains about five and twelve years of age could be obtained. This leaves the series incomplete.

Unfortunately, it was not known until the investigation was nearly finished that the method used for sulphur determination gave low results. This vitiates to a certain extent the reports on the various forms of sulphur, the sulphatids, and because of the methods of calculating the data, the cerebrosides, and the undetermined cholesterol. It was planned to make direct cholesterol estimations, but the series took so much longer than expected that these estimations were omitted.

Analyses 7 and 10 were made together. A combination of circumstances tendered their phosphatid determinations somewhat unreliable. If the solutions to be precipitated by chloroform and hydrochloric acid become too warm and are allowed to stand too long, the phosphatids are incompletely precipitated. This gives not only an error in phosphatids, but, by difference, in 'cholesterol, etc' and in extractives.

Many ways were found of improving the method after beginning this series, but they could not be adopted because of the effect on comparisons of results. One always sees many ways of improving an investigation after it is finished, and that is unusually true of this investigation.


Description of Material

Dr. H, Gideon Wells, of the Pathological Department of the University of Chicago, very kindly arranged to help us in this investigation. Without his cooperation, this series would have been very incomplete.

Upon receipt of a brain the meninges and blood were removed from the brain and it was divided into forebrain, cerebellum, and brain stem, and each division weighed. Samples were then taken and placed in enough 95 per cent alcohol to make the concentration 85 per cent alcohol. The specimens were as follows:

Three-month fetus. Male. Two three-month fetuses, referred to as normal, were united in order to furnish material enough for one good analysis. These brains were not divided into forebrain, cerebellum and brain stem.

Seven-month fetus. Female. The mother of this stillborn fetus entered the hospital five days before the dehvery with signs and symptoms of placenta praevia. A brain of this age also give^ too small amounts if separated into divisions, so such separation was not made.

One-month child. Male. This child died of bronchopneumonia. The forebrain was separated from the rest of the brain, the cerebellum and brain stem were analyzed together because there was not enough in either to make a satisfactory separate analysis.

Three-month child. Male. Died of bronchopneumonia and marasmus.

Eight to twenty-four month child. Male. Though there was no record of this child having been abnormal, the brain was found to be decidedly underweight for the two-year age reported. The child may not have been two years old, but younger. More Hkely it was subnormal.

Twenty-one year adult. Male. Died of pneumonia. The autopsy did not take place for three days after death, but the weather was cool, so the brain was in good state of preservation when received.

Thirty-three year adult, (negro). Male. Died of acute pneumonia. No other disease was present.

Thirty-five year adidt (Hungarian). Male. Cause of death not reported. Brain was very high in solids, but not pathological in any evident way.

Sixty-seven year adult. Male. Died of tuberculosis.

The weights of the different divisions obtained from these brains were as follows :

Whole brain: Weights of divisions in grams

Whole brain. Forebrain. . .

Left

Right

Cerebellum. . Brain stem. .


FETUS

3

MONTHS


FETUS

7

MONTHS


CHILD

1 MONTH


CHILD

3

MONTHS


CHILD'

8

MONTHS


ADULT

21 YEARS


ADULT

33 YEARS


ADULT

35 TEARS


17.08


119.0


457.4


585.2


492.5


1122.4


1221.3


1158.3

395.0


514.0


409.0


950.0


1026.0


986.0


200.0


263.0


206.0


485.0


516.0


510.0


195.0


251.0


203.0


465.0


510.0


476.0


(37.4)4


42.6


48.2


111.4


130.6


110.8


(25.0)4


28.5


35.3


61.0


64.7


61.5


ADULT

65 TEARS


1297.9

1075.0

535.0

540.0

145.4

77.5


^ See section on Limitations for explanation.

Analyzed together because of small amounts of each.

Discussion of Results

Water and total solids

The water determinations show that though the absolute amount increases (table 12, fig. 1), the percentage of this constituent decreases continually (table 10) until growth is completed. The relative amount of water present is an indication of the rate of activity. Water, like the inorganic salts and the simpler organic substances (table 10), decreases relatively rather regularly with the approach to adult condition and its decrease in rate of metabohsm.


The percentage of total solids of course varies inversely with that of water. The increase is largely due to the formation of the colloidal substances. They increase in absolute amounts (table 12, fig. 1) and in percentage (table 10), while the simpler molecules, as a rule, decrease in percentage, but increase in absolute quantity. It will be noticed from table 13 and figure 2 that the solids are formed most rapidly soon after birth; at least 0.5 grams a day are then being added. This coincides with the period of most rapid myelination.


It does not necessarily follow that this is the time of greatest protoplasmic activity, because under other conditions the products of the reaction may be removed, while during the period of myelination a part may form the sheath.

It needs to be remembered that the substances produced in myelination are not to be thought of as active protoplasmic compounds in the same way as the extractives, certain lipins, and nucleoproteins. This is true whether one considers the sheath as nutritional or insulating in function. In comparing nerve activity with other tissues, it would probably be more exact, therefore, to use data on the axis cylinders and not the whole nerve (Donaldson, '16).


Wt in gms.


80


72


64


56


48


+0


32


i+


16


1 1 1 1 1



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r totems ^*^ -^


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y y x


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/ ^ x^


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24- 32

1/ me In months Fig. 1


40


48


56




Milligrams added per day


lay



1 M 1 M 1 1 11 1 1 1 M 1


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"yriit



100



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77


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Daraclives


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12 16 20

T/me in months Fig. 2


24


28


Phosphatids

Lecithin (MacArthur and Darrah, '16), cephalin (MacArthur, '16), sphingomyelin and myeUn are the principal phosphatids found preformed in the brain. Some or all of these compounds are present from very early fetal life (table 1). They gradually increase (table 12) until myelination becomes rapid, then they are formed at the maximum rate of 0.1 gram per day (table 13). They continue to be formed rapidly until two years of age; after this the rate decreases to adult age. During adult life they probably increase very slowly and are one of the colloidal factors to be considered in retarding metabolism in old age.

We have some reasons for beUeving that lecithin is the phosphatid largely found in the nerve cells (Cowdry, '14). It looks as though it were rather closely associated with the nucleoproteins in carrying on vital activities. Cephalin is probably present in both the cells and axis cylinders, though more largely in the latter. Very little is known about sphingomyelin, but it it is probably largely to be found in the sheaths. It would be very interesting to study the increase in each of these phosphatids during growth.

Lecithin, and especially cephalin, because of their auto-oxidation characteristics, are believed to be closely related to nervetissue oxidation (Signorelli, '10; MacArthur and Jones, '17).

Cerebrosides

Phrenosin (Levine and Jacobs, '12) and kerasin (Rosenheim, '13), the two brain cerebrosides, may be parts of an unstable complex made up of sulphatid, phosphatid, and cerebroside. If this is true, the data in this paper would indicate that with growth this complex increases in complexity (fig. 1), because the cerebrosides as analyzed do not appear until birth (tables 2, 5, and 8), when myelination becomes the dominant brain activity. This may mean that they are in some way dependent on the presence of other constituents for their production. They are peculiar in the rapidity with which they assume such a prominent place in developing nerve tissue.

The cerebrosides are probably more directly related to sheath formation than any other constituent (Smith and Mair, '12- '13). Their maximum rate of formation does not occur as early as in the case of the other brain constituents (at four months instead of at birth) (table 11). Then about 0.025 gram are added each day.


Sulphatids=

Because of uncertainty concerning the sulphatids found in the brain, the report for this constituent is open to question. It is assumed, however, that it is a cerebroside and phosphatid fastened together by a sulphate radicle (Koch, '10). The sulphatids are very closely related to the cerebrosides in physiological function and anatomical distribution. The sulphatids seem to be more fundamentally necessary because they are found earlier (table 10). They may be related to conductivity in axis cylinders. Small amounts are present in very early fetal life (tables 1, 4, and 6). Soon after birth the amounts formed are greatest (table 12), but there is no time during life when this compound is not being produced. Probably it is concerned in the rivalry between structure and function, helping the former to victory in stability of activity, and finally in death. This is one of those substances so necessary for highly specialized brain work, but so detrimental to continued growth.

Proteins

The most important protein of the brain, because of its greater lability, is probably nucleoprotein a (McGregor, '17). One would expect it to be associated with the vital functions. It probably is a combination of the globulin a, globulin b, and the nucleoprotein of an earlier worker (Halliburton, '94). Nucleoprotein b is mUch more stable and may be the protein of the chromatin and Nissl bodies, thus related to the hereditary quality of the nerve cell. Neurokeratin is stable and probably is connected with the structure of the nerve sheaths. It is highly important to know how these different proteins increase with growth, but we have only indirect evidence of what these changes are. From the data on total protein, protein phosphorus and protein sulphur (table 11), we can get an idea, of what is happening, however, Thus indirectly we can suggest that neurokeratin approaches a maximum percentage at two years of age, but is present in very small amounts in even early fetal life. Nucleoprotein b is probably present in largest percentage amounts inearly fetal life, but continues to increase in absolute amounts (table 12) until maturity, when there is about twice as much as of nucleoprotein a and half as much as of neurokeratin (McGregor, '17). Nucleoprotein a possibly is always present, but probably is largest in percentage amounts when nerve growth and activity are greatest. It would not do even to guess how these last two proteins are distributed in the brain.

The total protein curve (fig. 1) indicates that some particular protein (possibly nucleoprotein b) is an especially important factor in the subsequent growth of the brain. It seems to lead in the increases that take place.

Extractives

The separation of extractives into organic and inorganic, as given in the data, is of but little value because of the fact that such a separation, based on the solubility of organic constituents in alcohol and the insolubility of the inorganic ones in alcohol (or on the residue after ignition), is very unreliable. The data given are merely suggestive. Howev-er, the determination of total extractives is rather accurate. Inosit, urea, leucin, tyrosin, taurin, hjTDOxanthin, and peptones are a few of the organic substances present in this fraction. In general it may be stated that the larger the percentage of these simpler crystalloidal molecules, the more rapid the metabolism and the younger the tissue. Various inorganic salts of sodium, potassium, ammonia, calcium, magnesia, and iron have about the same significance. While the rate of growth is high, these constituents are present in larger percentage amounts (table 11), but with a decrease in rate of development they rapidly decrease in rate of formation, until after two years of age they are but very slowly increased in absolute amount (table 12).

They are present in larger amounts in cells than in axis cylinders. Potassium salts and chlorides are supposed to be related to nerve conductivity (Alcock and Lynch, '11).

In drawing conclusions concerning the rate of activity of nerve tissue from the percentage amounts of extractives, one needs to remember that it may be more accurate to leave the sheath substances out of the reckoning. The calculations would then be based on the assumption that but three-fifths of total solids are directly concerned.

Sulphur compounds

By estimating sulphur in the various fractions we obtain information about the relative amounts of several important brain compounds. The lipin sulphur is a measure of the amount of sulphatid, and is therefore largely concerned in sheath development. In consequence it obtains a maximum rate of formation at about three months of age. Protein sulphur represents the amount of cystin in protein combination. Cystin is present in much smaller amounts in the nucleoproteins of the brain than in neurokeratin. So protein sulphur gives us a rough estimate of the amounts of neurokeratin being formed. It will be noticed that this form of sulphur follows very closely myelin formation (table 10). Neutral sulphur may represent an intermediate oxidation product of cystin or possibly taurin; an increase in this form might indicate a decreased oxidative ability in the cells (W. and M. L. Koch, '13). Of the total sulphur, neutral sulphur forms a greater portion in the younger tissue, while the portion of protein sulphur increases with age. The inorganic sulphates are the final sulphur oxidation products. They remain rather constant in percentage amounts (table 11). This may be due to the fact that, they are readily eliminated from the cell. Total sulphur increases in percentage of fresh tissue until adult age, then remains rather constant. The maximum addition, of about 3 mg. per day, takes place at about three months of age (table 13).

Phosphorus compounds

The amount of phosphorus in the lipins is used to determine the amount of the phospho-lipins. It is added most rapidly at birth (table 13, fig. 2) (at least 3.5 mg. per day), but like most of the other constituents, its rate of addition per unit of reaction substances is greatest in the youngest tissue (tables 14 and 15, fig. 3).


Percentage Increase Per Day


Fig. 3


28


32


36


Protein phosphorus represents the amount of nucleoprotein. This probably closely approximates the changes in the activity of the protoplasm, both nucleus and cytoplasm. This form increases in amount with age, but the percentage changes less than any other kind.


Under the heading of organic phosphorus is included a number of comparatively simple compounds of phosphorus with organic radicles. There is no definite separation of this group from the following one (Emmett and Grindley, '06). It is representative of the amount of protein metabolism and bears a definite relation to the two colloidal forms of phosphorus mentioned above.

Inorganic phosphates are also a measure of rate of activity. In fact, the sum of these last two forms the best criterion of rate of phosphorus metabolism. It is worth noticing that in terms of percentage of total phosphorus the amounts of colloidal phosphorus compounds are increasing with growth, while those of the crystalloidal forms are decreasing (table 11). In fresh tissue the percentage of extractive phosphorus increases slightly, then decreases to a certain extent; but these small variations from a constant may not be significant. The figures, however, indicate rather definitely that these simpler forms of phosphorus do not closely follow the change in percentage of water, as one would expect if the quantity of fluid determined the amount of extractives. From table 11 it is evident that extractive phosphorus, like other extractives, markedly decreases in the percentage of total solids.

Comparison of forebrain, cerebellum, and brain stem

In the adult brain the cerebellum contains the largest percentage of water, the forebrain slightly less, the brain stem least. A high percentage of solids indicates slower but more highly dfferentiated metabolism; therefore the cerebellum acts fastest, while the brain stem is most stereotyped. During growth the rate of increase in the percentage of solids is in the following order, brain stem (table 4), forebrain (table 1), and cerebellum (table 7) ; this is, of course, to be expected.

In the stem the phosphatids are in larger amounts (table 5) and are probably laid down earlier than in the other two divisions of the brain. The cerebellum contains the smallest amount of this group of constituents (table 8) , indicating that it is probably less highly specialized than other parts.


The cerebrosides and sulphatids are present in slightly larger amounts in the stem (table 5) than in the forebrain (table 2), but in very much larger quantities than in the cerebellum (table 8). This would indicate that one of the main differences in chemical constitution between the cerebellum and the rest of the brain is in the amount of meduUation.

Cholesterol, etc., is found most largely in the stem and least in the cerebellum.

The total lipins are not only largest in amount in the stem (table 5) and least in the cerebellum (table 8), but possibly are formed slightly earlier and at a more rapid rate in the same order.

In all divisions the proteins show in general variations exactly opposite to that of the lipins. Thus with age there is a decrease in percentage of solids (tables 2, 5, and 8). The total proteins exist in but slightly different percentages in the different parts of the fresh tissue (tables 1, 4, and 7), and they seem to be formed at approximately the same rate in all.

In an attempt further to analyze the meaning of these variations in protein content, the data frpm protein sulphur and protein phosphorus are of value. It is probable that the greater amount of protein -sulphur is in neurokeratin, a constituent of supporting tissue, while the protein phosphorus is very largely present as nucleoprotein b (0.6 per cent P), only a relatively small amount being present as nucleoprotein a (0.11 percent P). (The percentage amount of the former, 10 per cent, is about twice that of the latter, 5 per cent in adult tissue.) From tables 1, 4, skid 7, then, it will be noticed that there is more than twice as much nucleoprotein in the cerebellum as in other parts of the brain. This difference prevails throughout growth. The stem and forebrain differ but little in this respect. On the other hand, protein sulphur (neurokeratin) is a little greater in the brain stem than in the forebrain or cerebellum. To judge from these data, one might state that the number of nuclei, or at least the amount of nuclear material, is considerably larger in the cerebellum, while the amount of supporting tissue is not very different in the various parts of the brain. Concerning the extra nuclear proteins (nucleoprotein a) it is difficult to make more than a guess — that they would vary with the other functioning protein (nucleoprotein h).

Neutral sulphur is a rough measure of the amount of protein metabolism taking place. It is rather striking that the greatest rate of protein metabohsm is in the forebrain (table 2) and cerebellum (table 8) and least in the brain stem (table 5). The rate in all remains rather constant in spite of the fact that the amount of protein increases with age.

Throughout growth the total extractives are present in much larger amounts in the cerebellum (table 8) than in the rest of the brain. The stem has a slightly larger percentage than the forebrain. In all divisions the maximum addition per day is reached at about three months of age (tables 2, 5, and 8, fig. 2). After this there is a slow decrease in amount of daily additions till old age, indicating that aging is a regular decrease in rate of metabolism. The larger part of the extractives in the cerebellum is composed of inorganic constituents. This is probably to be expected from the larger protein content in this division of the brain.

The total sulphur increases more rapidly and attains a somewhat greater percentage in the brain stem than in the forebrain (table 1) and a considerably greater percentage than in the cerebellum (table 7). This seems to be largely due to the relatively larger amounts of lipins in each division in the order named. The inorganic sulphates gradually increase in each division at about the same rate.

The amount of total phosphorus does not differ much in different parts of the brain, but the lipin phosphorus is greater in the stem (table 5) and forebrain (table 2) than in the cerebellum (table 8). The inorganic phosphates seem to be closely related to nucleoprotein h, because they are represented to a much greater extent in the cerebellum than in the other divisions of the brain.


General Discussion

1. Dominance of the nervous system

There seem to be no facts presented in this paper that are inconsistent with the theory that the chromosomes are very important in the early differentiation of cells. In fact, the data suggest that nucleoproteins (tables 10 and 11, fig. 1) then phosphatids and simple extractive molecules dominate in the youngest tissue. It is probable that there is a metabolic gradient in the fertilized cell that is important in determining which will be the head end of the organism (Child, '12). Very early in growth nervous tissue differentiates in this head region. Because of this early formation, much of the later development in other parts of the body is rather dependent on the nervous system. It needs to be emphasized that this dominance of one substance over another (or one organ over another) is but relative. Most of them are developing together, but their influence on each other is very different. Very probably growth consists in the formation of continually larger quantities of the respective cell constituents in a more or less definite order, commencing with the nucleoproteins (table 11, fig. 2) of the chromosomes. In the brain there is rapid formation of certain substances, then the presence and formation of the substances influence the rate of formation of another substance, this another, and so on till all have come into adjustment with the new conditions. While these changes are occurring in the brain, and partly because of them, other areas of differentiation are split off, which are to become other organs. Then in these areas a similar cycle of changes will occur. Probably each of the organs has periods of maximum growth. When such unusually large amounts of material are being formed rapidly, in comparison with the rate of formation at other periods of growth, we get an irregularity in the main curve of growth that produces a so-called growth cycle.

During growth substances are regularly coming to the various organs through the blood. We do not now believe that the amount of either these food substances or the oxygen determines the rate of growth, though they do influence it. The cells in any organ seem to grow somewhat in unison, but they are influenced by cells of other organs, both through the blood and through the nerves. There is no doubt that each organ directly influences the growth of every other in both of these ways. Certain glands secrete substances and discharge them into the circulation that have a disproportionately large effect in influencing growth in most tissues. But it is not correct to assume that growth is determined by these; it is only altered by them. Growth seems to be a general cell process, and these substances simply change the rate of this general cell development.

The growth of the brain is probably less under the influence of internal secretions than other organs. Indeed, there is strong evidence that the secretions are largely under the influence of the nervous system. There is no indication of internal secretions in simple organisms, yet these organisms have a similar form of growth.

2. Relation of these data to four physiological facts

In any interpretation of brain growth it is necessary to keep in mind several important facts:

1. A larger amount of early differentiation occurs in nervous tissue than in other tissues. Though this fact is associated with some definite differences that exist in the fertilized cell, the subsequent chemical supremacy is important in evolving the marked specialization. The early formation of colloidal substances such as the nucleoproteins, phosphatids, and sulphatids (table 10) give a peculiarity to young nerve tissue that permits it to influence rather markedly the development of other tissues. It is more than theoretical to assume that the early start of nervous tissue allows it to differentiate more than other parts of the body.

2. The nerve cells, unlike other cells, do not regenerate. It is very probable that a nerve cell if tested for regenerative power early enough in its growth would regenerate just as other undifferentiated tissues do. It very soon reaches a stage, however, w^hen it is so highly specialized by the elaboration of colloidal complexes (table 11) that regeneration is impossible.


3. The number of nerve cells remains constant. Rather early in growth, probably as early as the seventh fetal month (table 10) the number of nerve cells is largely determined. No amount of functioning produces an increase. This would indicate that the chemical changes in brain growth are fixed within rather close limits. It also suggests that development in the brain is essentially different than elsewhere. Probably the main processes are determined at the time of the formation of the cells. The organization is such, however, that smaller but no less important (speaking physiologically) change occurs during later activity.

4. Nervous tissues remain constant in composition under conditions that markedly alter many other tissues. The chemical composition of the nervous system must be related to this supremacy. The large amounts of several of the lipins (table 10) seem to be of importance. Though the large amount of colloidal material in the form of lipins and proteins is often supposed to be indicative of slower metabolism and a lack of dominance (Child, '11), the chemical condition in the brain would suggest that colloidal structure is equally important wdth the rate of metabolism in maintaining dominance. It te conceivable that in the case of the brain its early importance, due to the high rate of metabolism, should be maintained through specialized activity, even when this rate is no longer greater than the rate in other tissues. The highly specialized nerve fiber and cell are made of many compounds that are but slightly available to other tissues, because such substances are in almost irreversible equilibrium with metabolizing substances elsewhere.

Another factor that is undoubtedly involved is the selective nature of the membranes surrounding the cells of the nervous system. Very probably such membranes or surfaces are much more common than is supposed, thus providing means of keeping the various tissues in equilibrium with each other. If the membranes in the nervous system are more nearly irreversible than in other parts, the condition exists that is favorable for maintenance under circumstances that use up other tissues.

No other tissue has a chance to supplant the nervous system with its highly specialized pathways to all parts of the body.


It does not need to depend on its rate of activity for supremacy; the conditions it has developed for its maintenance assure this dominance though the means used for obtaining it no longer exist.

3. Concerning three periods of growth

There are three distinct processes to be distinguished in brain development. The one that takes place first is cell division. This is probably almost completed at the time of the sevenmonth-old fetus. It is worth noting that there is no evidence of sheath development up to this point. There are no cerebrosides; the amounts of sulphatids are increasing slowly. The phosphatids do not show any dominance. The relatively large amounts of protein, and especially the nucleoproteins, suggest that chromosome formation is very prominent. The large quantity of extractives emphasizes the fact that metabolism is very rapid during this period.

From the seven-month fetus to about the time of birth, cell growth is the important process. At this time the phosphatids come into prominence, while the proteins and extractives retain their earlier dominance. Cholesterol, though present, is not important. The same is true of sulphatids, while the cerebrosides are lacking entirely or are present in but small amounts. These changes arfe what one would expect in growing cells and enlarging axis cylinders. How important the axis cylinders are in accounting for brain growth is indicated by the fact that about two-fifths of the brain consists of them.

The third period is that of meduUation. It becomes prominent soon after birth, reaches its maximum a few months after birth, and slowly decreases in importance. The sheaths comprise about two-fifths of the brain substance, so it is not surprising that cerebrosides, sulphatids, and some of the phosphatids become so prominent. The proteins and extractives are skill of importance, but thoroughly masked by the new process. It is probable that when the nerve cells reach the stage at which conditions are proper for sheath formation, there is a release of energy or an alteration in metabolism through the extension of the field of local dominance that is large enough to amount to a slowing down temporarily of the rate of loss of growth power.

By comparing these results with those obtained in a growth series on the brain of the albino rat (W. and M, L. Koch, '13) a great similarity is evident. The nature of the process, the division into periods, the relative amounts of the various constituents, and their order of development are much alike. The main differences are found in the larger percentage amounts of lipins, with a corresponding decrease in proteins and a great lengthening of the periods of growth. Thus the changes occurring in the rat brain are much more rapid than in human brain, but the rat brain does not attain quite the same degree of differentiation. By comparing the data in the two series for extractives as a whole, and the various extractives, no marked differences are evident, indicating that the changes in rate of metabolism with growth are similar in both, though the time necessary to change from one corresponding physiological age to another in the rat is probably but about one-thirtieth of that in the human.

4. Nature of the growth process

One of the most interesting points which these data raise is that of the nature of the growth process in nervous tissue. The curves show that the brain as a whole, as well as each of the individual substances or groups of substances (tables 12 and 13, figs. 1 and 2) estimated, increases slowly in absolute amounts per unit of time during the first part of development. Later the increase is larger, and is then followed by a period when the amounts are continually smaller. If, however, one observes the curve for the amount added per unit mass of substance during a given period of time (tables 14 and 15, fig. 3) it is seen that the rate of addition is greatest in the youngest tissue. This rate of addition diminishes most at first, then more slowly, and is followed by a somewhat greater comparative rate of loss of growth power. The first curves (absolute amounts) are smilar to those reported for growth of the whole organism (Robertson, '08). Such curves are by some authors supposed to indicate that the process they represent is an autocatalytic one (a chemical reaction that increases in speed at first because of the catalj^zing effect of a product of the reaction, and then slows down, because of the retarding effect of larger amounts of a product of the reaction and decrease in the original substance). Can the second curve, however, be reconciled with this theory? From this curve it would seem that the rate of reaction is fastest at first and slows down continuously during growth (Meyer, '14).

There is no inconsistency between these two facts (1st, that the absolute amount of substance added is greatest during the middle period of development; 2d, that the amount of substance added per unit mass is greatest at an early period of development) if we make certain assumptions. It is necessary to assume that all or nearly all of the substance (or group of substances, or total brain, or total organism) is a product of this reaction or determined by some other reaction. The substances .weighed are entirely (within limits of error in data) the product of something not weighed or too small to make a significant difference in the weighing. This means that the cytoplasm, and probably nucleus (Loeb, '06), is a product of something else either present and very small, or absent, or not weighable. The easiest interpretation of this difficulty is to invoke the aid of vitalism. This would furnish our unweighable element that determines the growth of even the protoplasm. However, if something a little more substantial is required, one can assume the presence in the brain (or in some other part of the body connected physiologically with the brain) of a very small amount of a substance that in some way determines the formation of all other substances in the tissue (or organism) considered. This substance probably would decrease during growth. One or more of its products would catalyze its effect on formation of other substances. It might exert its control over other reactions by operating over a longer period of time or by having an unusual nature. It is conceivable that a hormone or enzyme-like compound might have such unlimited power. This would assume that at fertilization, or soon after, this substance was made, and that subsequent development is essentially a product of it. Aging would mean the using up of this substance or an interference with its rate of reaction. Any variations in growth would be due to alterations in the general growth produced by other substances or conditions.

Though the hormones and the active principles in the internal secretions are very popular these days, it seems rather too much to expect that one and only one of them possesses such vitalistic properties. It seems more rational to suppose that they are active in bringing about alterations in growth, but that the main process is independent of them. There is practically no evidence that such substances are determiners of growth in unicellular organisms. If one accepts the autocatalytic theory, it seems necessary to give up the protoplasmic theory, for protoplasm, too, should be simply a product and does not possess growing power. As a result of this and other work, it can be stated with considerable certainty that neither nucleus nor cytoplasm causes growth to take place autocatalyticaUy, If one believes that the evidence for the living, growing nature of the protoplasm as a whole is well founded, chemical autocatalysis should be discarded. The data agree so well with the theory, however, that there must be some reason why a substance in a living organism, as well as the whole tissue or organism should add largest absolute amounts of substance (table 13, fig. 2) during the middle of the growth period. It is worthy of mention, though it is probably not a fundamental explanation to say that protoplasm has an inherent power, when unimpeded by the lack of food or too much of the products of its activity, to increase in a geometrical ratio. As is well known, bacteria and unicellular organisms increase in number and in absolute weight (when retarding factors are small) in this 1, 2, 4, 8, 16 ratio. If such numbers are plotted against tune, the first part of the S-shaped curve is obtained. The latter half of the curve is produced through decreasing the geometrical ratio by the retarding effect of lack of food or production of toxic products. By analogy, such a curve should be produced in a multicellular organism, through the division and development of the cells producing it. It is thus seen that the essential characteristics of autocatalysis are the necessary result of cell division in an imperfect environment. Of course, one of the reasons why cells do not divide so often when there are more of them in a more unfavorable medium is that the individual cells do not grow to the dividing stage so quickly. However, one can apply the geometrical ratio idea to the development of the individual cell if that is found to increase in absolute weight fastest during the middle period of growth. In fact, it is rather to be expected that such would be the form of its growth, without its being in any way related to autocatalysis. For if the protoplasm formed on cell division is thought of as a unit of protoplasm, it would form two units in a certain period of time; then these two would form four, and so on through the geometrical series, if no retarding factors were present. But there are undoubtedly such factors, so we get essentially the autocatalytic phenomenon. The size of the cell, the relation of size of the nucleus to that of the cytoplasm, the amount of cell differentiation, complexity of colloidal substratum of cell are large factors in determining this form of growth. There seems to be a physiological state that is rather definite for any kind of cell, which, unaltered, tends to make the cells increase. One sees the necessity, granting the power of protoplasm to produce more material like itself, in an increasingly unfavorable environment, for the S-shaped curve of growth. This is independent of the question why growth takes place; it is true, irrespective of the nature of the growth impulse. It is probably not wise, however, to speak of such growth as autocatalytic, because it probably does not have a chemical autocatalytic basis. Though enzymes seem to play a part in it, it is not necessarily enzymic at all, much less autocatalytic and monomolecular. Probably anything that can increase geometrically, put under progressively less favorable conditions, whether living or not (say, the growth of a crystal in a slightly supersaturated solution), would give an autocatalytic form of increase.

Summary

1. During growth the proteins, phosphatids, sulphatids, cerebrosides, cholesterol, and total solids increase in percentage amounts. There is but slight change in the percentage of extractives, either organic or inorganic. Water decreases regularly to maturity.

2. In percentage of solids each of the lipins increases rapidly until a few months after birth, then more slowly until maturity. (Cerebrosides are not present in free condition till about the time of birth.) The proteins slowly decrease in percentage of solids with growth, but the extractives, both organic and inorganic, very rapidly decrease.

3. At birth most of the brain compounds are being laid down most rapidly. Cerebrosides and sulphatids, however, have the greatest daily additions about three months after birth.

The following amounts, in milligrams, are added per day in a new-born child: water 3270, solids 494, lipins 165, phosphatide 85, cholesterol + 70, sulphatids 7.7, cerebrosides 1.9, proteins 186, organic extractives 100, inorganic extractives 44, sulphur 2.3, phosphorus 8.5.

4. The brain stem contains the largest percentage amounts of total solids, total lipins, and of each lipin, but the least protein, organic extractives, inorganic extractives, and water. The forebrain is not much different frQm the stem. The cerebellum, however, varies largely. In development, the brain stem differentiates chemically first and fastest. The forebrain follows closely. The cerebellum never attains to such a high degree of specialization.

The data may indicate that the cerebellum is not only the slowest and least meduUated, but that it remains the youngest division of the brain with the highest rate of metabolism.

5. It is suggested that, because of the early marked chemical differentiation of the brain in the head end of the organism, further development is greatly influenced by the central nervous system.

6. An attempt is made to correlate the data obtained with the early differentiation of specialized nerve tissue and its constancy in number of cells and composition.

. 7. The chemical analyses agree that brain growth consists of 1) increase in the number of cells; 2) their growth, including that of the axis cylinders, and 3) medullation.


8. The data show that, though the absolute amount of each of the constituents added is greatest during a middle period of growth (birth), the greatest rate of growth is in the youngest tissue. It is not believed that brain growth is necessarily autocatalytic. The whole brain, as well as each constituent, increases with development, as is to be expected if it is assumed that a given mass of protoplasm makes more material like itself in an increasingly less favorable environment. It seems to be a logical necessity, not even dependent upon life.


Literature Cited

Alcock, N. H., and Lynch, G. Roche. 1911 On the relation between the physical, chemical, and electrical properties of the nerves. III. Total ash, sulfates, phosphates. J. Physiol., vol. 39, p. 402.

Child, C. M. 1911 A study of senescence and rejuvenescence based on experiments with Planaria dorotocephala. Arch. Entw. Mech. Org., vol. 31, p. 571.

1912 Studies on the dynamics of morphogenesis and inheritance in experimental reproduction. IV. Certain dynamic factors in the regulatory morphogenesis of Planaria dorotocephala in relation to the axial gradient. Jour. Exp. Zool., vol. 13, p. 103.

CowDRY, E. V. 1914 The comparative distribution of mitochondria in spinal ganglia cells of vertebrates. Am. Jour. Anat., vol. 17, p. 1.

Donaldson, H. H. 1916 A preliminary determination of the part played by myelin in reducing the water content of the mammalian nervous system (albino rat). Jour. Comp. Neur., vol. 26, p. 443.

Emmett, M. D., and Grindley, H. S. 1906 The chemistry of flesh (third paper). A study of the phosphorus content of flesh. J. Am. Chem. Soc, vol. 28, p. 25.

Halliburton, W. D. 1894 The proteids of nervous tissues. J. Physiol., vol. 15, p. 90.

Koch, M. L. 1913 Contributions to the chemical differentiation of the central nervous system. I. A comparison of the brain of the albino rat at birth with that of the fetal pig. J. Biol. Chem., vol. 14, p. 267.

Koch, W. 1910 Zur Kenntnis der Schwefelverbindungen des Nerven Systems. II. Uber ein Sulfatid aus nerven Substance. Z. Physiol. Chem., vol. 70, p. 94.

Koch, W., and Koch, M. L. 1913 Contributions to the chemical differentiation of the central nervous system. III. The chemical differentiation of the brain of the albino rat during growth. J. Biol. Chem., vol. 15, p. 423.

Koch, W., and Mann, S. A. 1907-08 A comparison of the chemical composition of three human brains at different ages. Am. J. Physiol., vol. 36, p. xxxvi.

Levene, p. a., and Jacobs, W. A. 1912 On sphingosine. J. Biol. Chem., vol. 11, p. 548.

LoEB, J. 1906 Weitere Beobachtungen iiber den Einfluss der Befruchtung und der Zahl der Zelkerne auf die Saurebildung im Ei. Biochem. Z., vol. 2, p. 34.

MAcARTHtfR, C. G- 1914 Brain cephalin: I. Distribution of the nitrogenous hydrolysis products of cephalin. J. Am. Chem. Soc, vol. 36, p. 2397.

MacArthur, C. G., and Darrah, J. E. 1916 Nitrogenous constituents of brain lecithin. J. Am. Chem. Soc, vol. 38, p. 922.

MacArthur, C. G., and Jones, O. C. 1917 Some factors influencing the respiration of ground nervous tissue. J. Biol. Chem., vol. 32, p. 259.

McGregor, H. H. 1917 Proteins of the central nervous system. J. Biol. Chem., vol. 28, p. 403.

Meyer, A. W. 1914 Curves of prenatal growth and autocatalysis. Arch. Entw. Mech. Org., vol. 40, p. 497.

Robertson, T. B. 1908 On the normal rate of growth of an individual and its biochemical significance. Arch. Entw. Mech. Org., vol. 25, 581.

Rosenheim, O. 1913 The galactosides of the brain. I. Biochem. J., vol. 7, p. 604.

SiGNORELLi, E. 1910 Tiber die Oxydation-processe der Lipoide des Riicken marks. Biochem. Z., vol. 29, p. 25.

Smith, J. Lorrain, and Mair, W. 1912-13 The development of lipoids in the brain of the puppy. J. Path. Bact., vol. 17, p. 123. The lipoids of the white and gray matter of the human brain at different ages. J. Path. Bact., vol. 17, p. 418.


TABLE 1

Forebrain: Constituents in -percentage of fresh tissue



FETUS

3

MONTHS

(13)1


FETUS

7

MONTHS

(12) =


CHILD

1

MONTH

(11)


CHILD

3

MONTHS

(V)


CHILD

8

MONTHS

(4)3


ADULT

21 YEARS

(23)


ADULT

(33)

YEARS

(28)


ADULT

35 YEARS

(3)


ADULT

67 YEARS

(22)


Water


91.91 8.09

1.04


0.16 0.58


90.56 9.44

1.24


0.27 0.97


88.09 11.91

1.94


0.25 1.53


87.03 12.97

(1.74)4 .30 .50 1.70


85.81 14.19

3.17 0.49 0.50 0.91


77.32

22.68

5.68 1.29 1.84 3.63


77.06 22.94

6.00

1.28 0.66

4.81


72.85 27.15

6.86 2.58 1.72 4.08


78.47


Solids


21.53


Phosphatids

Cerebrosides

Sulphatids

Cholesterol


6.54 1.72 1.35 2.55


Total lipins


1.78


2.48


3.71


4.24


5.06


12.44


12.75


15.23


12.15


Total proteins

Organic extractives

Inorganic extractives


3.77

1.54 1.00


3.98

1.77 1.21


4.57

2.44 1.19


5.29

2.38 1.06


6.09

2.01 1.03


8.03

1.19 1.02


8.11

1.11 0.96


8.99

2.03 0.91


7.53

0.88 0.96


Total extractives. .


2.54


2.98


3.63


3.44


3.04


2.21


2.07


2.94


1.84


Lipin suiphur... . Protein sulphur. Neutral sulphur. Inorganic sulphur


0.003 0.026 0.015

0.001


0.005 0.028 0.018

0.002


0.005 0.033 0.022

0.004


0,010 0.038 0.026

0.005


0.010 0.069 0.018

0.012


0.036 0.053 0.013

0.002


0.013 0.052 0.007

0.003


0.034 0.039 0.022

0.009


0.027 0.061 0.015

0.003




Total sulphur


0.045


0.053


0.064


0.079


0.109


0.104


0.075


0.104


0.106


Lipin phosphorus

Protein phosphorus ,

Organic phosphorus

Inorganic phosphorus


0.044 0.025 0.026 0.056


0.054 0.009 0.028 0.062


0.080 0.005 0.036 0.082


0.078 0.006 0.055 0.074


0.127 0.008 0.032 0.055


0.256 0.013 0.012 0.058


0.284 0.011 0.027 0.091


0.300 ,0.014 0.049 0.048


0.254 0.012 0.008 0.053




Total phosphorus..


0.151


0.153


0.203


0.213


0.222


0.339


0.363


0.411


0.327


1 The two brains of this age that were used for this analysis were not separated into cerebellum, forebrain, and stem, because the brains were too small to make good samples of these divisions. For purposes of comparison the whole brain was arbitrarily divided into cerebellum 10 per cent, brain stem 10 per cent, and forebrain 80 per cent.

2 The same is true of this brain.

3 See section on limitations.

4 See section on limitations for explanation of this low figure.



TABLE 2 Forebrain: Constituents in percentage of solids



FETDS


FETUS


CHILD


CHILD


CHILD


ADULT


ADULT


ADULT 35 YEARS


ADULT



3


7


1


3


8


21


33



67



MONTHS


MONTHS


MONTH


MONTHS


MONTHS


TEARS


YEARS




YE.\.RS



(13)1


(12)1


(11)


(V)


(4)1


(23)


(28)


(3)


(19)


(22)


Phosphatids. .


12.90


13.12


16.27


(13.40)1


22.33


25.06


24.67


25.26


25.34


27.19


Cerebrosides..






2.32


3.43


5.67


5.59


9.50


7.13


8.00


Sulphatids ....


1.95


2.85


2.06


3.87


3.53


8.12


2.89


6.32


6.90


6.26


Cholesterol. . .


7.24


10.28


12.86


13.09


6.39


16.02


22.45


15.01


18.47


15.03


Total lipins


22.09


26.25


31.19


32.68


35.68


54.87


55.60


56.09


57.84


56.48


Total proteins . .


46.56


42.15


38.31


40.78


42.91


35.40


35.36


33.10


32.27


34.97


Organic ex











tractives


19.04


18.75


20.52


18.35


14.18


5.23


4.85


7.46


6.12


4.08


Inorganic ex











tractives —


12.31


12.85


9.98


8.19


7.23


4.50


4.19


3.35


3.77


4.47


Total extrac











tives


31.35


31.60


30.50


26.54


21.41


9.73


9.04


10.81


9.89


8.55




Lipin sulphur.


0.039


0.057


0.041


0.077


0.071


0.163


0.058


0.127


0.138


0.125


Protein sul











phur


0.314


0.294


0.277


0.^7


0.483


0.235


0.225


0.146


0.279


0.279


Neutral sul











phur


0.187


0.183


0.190


0.195


0.128


0.057


0.029


0.081


0.022


0.070


Inorganic












sulphur


0.013


0.022


0.038


0.037


0.085


0.011


0.015


0.032


0.029


0.015


Total sulphur...


0.553


0.556


0.546


0.596


0.767


0.466


0.327


0.386


0.468


0.489


Lipin phos











phorus


0.538


0.563


0.676


0.597


0.886


1.136


1.017


1.110


1.120


1.179


Protein phos











phorus


0.306


0.100


0.041


0.045


0.056


0.055


0.048


0.052


0.063


0.057


Organic phos











phorus


0.322


0.300


0.306


0.422


0.225


0.053


0.117


0.180


0.226


0.035


Inorganic












phosphorus .


0.678


0.648


0.693


0.565


0.384


0.258


0.394


0.172


0.189


0.244


Total phos











phorus


1.844


1.611


1.716


1.629


1.551


1.502


1.576


1.515


1.598


1.515


iSee table 1.












TABLE 3

Forebrain: Weights of constituents in grams



FETUS


FETUS


CHILD


CHILD


CHILD


ADULT


ADULT


ADULT


ADULT



3


7


1


3


8


21


33


35


67



MONTHS


MONTHS


MONTH


MONTHS


MONTHS


TEARS


YEARS


YEARS


YEARS



(13)1


(12)1


(11)


(7)


(4)1


(23)


(28)


(3)


(22)


Brain


17.08


119.0


457.4


585.2


492.5


1122.4


1221.3


1158.3


1297.9


Forebrain..


13.664


95.2


395.0


514.0


409.0


950.0


1026.0


986.0


1075.0


Water


12.56


86.16


347.9


447.3


351.0


734.5


790.7


718.3


843.6


Solids


1.104


9.04


47.1


66.68


58.0


215.5


235.3


267.7


231.5


Phospha










tids —


0.1424


1 . 1808


7.660


8.940


12.96


53.95


61.56


67.64


70.33


Cerebro










sides...


0.0000


0.0000


0.000


1.542


2.00


12.26


13.13


25.44


18.49


Sulfa










tids....

0.0216


0.2568


0.980


2.570


2.05


17.48


6.77


16.96


14.52


Choles










terol.. .


0.0792


0.9232


6.043


8.738


3.72


34.48


49.34


40.24


27.42


Total











lipins


0.2432


2.3608


14.660


21.80


20.69


118.1


130.80


150.28


130.60


Total pro










teins


0.5152


3.7888


18.05


27.19


24.91


76.28


83.20


88.65


80.97


Organic











extrac










tives . .


0.2104


1.6848


9.638


12.24


8.22


11.31


11.39


20.02


9.46


Inor










ganic











extrac










tives...


0.1368


1.152


4.700


5.45


4.21


9.69


9.85


8.97


10.32


Total ex










tractives


0.3472


2.8368


14.338


17.69


12.43


21.00


21.24


28.99


19.78


Lipin











sul










phur. . .


0.0004


0.0048


0.020


0.051


0.041


0.342


0.133


0.335


0.290


Protein











sul










phur.. .


0.0035


0.0266


0.130


0.195


0.282


0.504


0.533


0.385


0.656


Neutral











sul










phur.. .


0.0021


0.0171


0.187


0.134


0.074


0.123


0.072


0.217


0.161


Inor










ganic











sul










phur...


0.0002


0.0019


0.016


0.026


0.048


0.019


0.031


0.088


0.032


Total sul










phur


0.0062


0.0505


0.253


0.406


0.446


0.988


0.770


1.025


1.140


473


TABLE 3— Concluded



FETUS

3

MONTHS

(13)'


FETUS

7

MONTHS

(12)1


CHILD

1 MONTH

(11)


CHILD

3

MONTHS

(7)


CHILD

8

MONTHS

(4)'


ADULT

21 YEARS

(23)


ADULT

33

YEARS

(28)


ADULT

35 TEARS

(3)


ADULT

(67)

YEARS

(22)


Lipin phosphorus


0.0060


0.0514


0.316


0.401


0.519


2.432


2.401


2.958


2.731


Protein









.



phosphorus


0.0034


0.0086


0.020


0.031


0.033


0.124


0.113


0.138


0.129


Organic phosphorus


0.0025


0.0266


0.142


0.283


0.131


0.114


0.277


0.483


0.086


Inor










ganic phosphorus


0.0077


0.0590


0.324


0.380


0.225


0.551


0.934


0.473


0.570

1


Total phosphorus


0.0206


0.1457


0.802


1.095


0.908


3.221


3.724


4.052


3.516


^ See table 1.


TABLE

Brain stem: Constituents in percentages of solids



FETUS

3

MONTHS (13)1


FETUS

7

MONTHS

(12)1


CHILD

1 MONTH

(14)2


CHILD

3

MONTHS

(20)


CHILD

8

MONTHS

(21)1


ADULT

21 YEARS

(27)


ADULT

35 TEARS

(18)


ADULT

67 YEARS

(26)


Phosphatids

Cerebrosides

Sulfatids


12.90 0.00 1.95 7.24


13.12 0.00

2.85 10.28


17.29 1.95 0.44

16.32


(25.86) 1.08 4.48

13.38


16.67 2.33 5.40

19.75


22.85

(0.81) 7.45 28.48


15.73

4.58

8.40

31.86


30.86 9.83 7.52


Cholesterol


11.87


Total lipins


22.09


26.25


36.00


44.80


44.15


59.59


60.57


60.08




Total proteins


46.56

19.04 12.31


42.15

18.75 12.85


39.21

17.31 7.66


40.55

8.61 6.04


40.52

9.50 5.83


31.41

5.45 3.55


29.96

5.78 3.69


32.01


Organic extractives. . . Inorganic extractives .


4.01 3.90


Total extractives


31.35


31.60


24.97


14.65


15.33


9.00


9.47


7.91


Lipin sulphur

Protein sulphur

Neutral sulphur

Inorganic sulphur


0.039 0.314 0.187 0.013


0.057 0.294 0.183 0.294


0.009

0.158 0.036


0.090 0.238 0.069 0.013


0.108 0.272 0.093 0.008


0.148 0.264 0.009 0.015


0.168 0.211 0.023 0.018


0.150 0.289 0.037 0.009


Total sulphur


0.553


0.556



0.410


0.481


0.436


0.420


0.485


Lipin phosphorus

Protein phosphorus. . . Organic phosphorus. . . Inorganic phosphorus.


0.538 0.306 0.322 0.678


0.563 0.100 0.300 0.648


0.674 0.138 0.252 0.595


1.100 0.068 0.119 0.435


0.753 0.064 0.168 0.425


1.035 0.041 0.064 0.314


0.778 0.052 0.184 0.199


1.343 0.044 0.147 0.238


Total phosphorus


1.844


1.611


1.659


1.722


1.410


1.454


1.213


1.772


1 See table 1. ^ gee table 4.


474


CHEMICAL CHANGES IN HUMAN BRAIN


475


TABLE 4 Brain stem: Constituents in percentage of fresh tissue


Water

Solids

Phosphatids

Cerebrosides

Sulfatids

Cholesterol

Total lipins

Total proteins

Organic extractives. . . Inorganic extractives .

Total extractives

Lipin sulphur

Protein sulphur

Neutral sulphur

Inorganic sulphur

Total sulphur

Lipin phosphorus

Protein phosphorus. . . Organic phosphorus. . . Inorganic phosphorus.

Total phosphorus


FETUS

3

MONTHS

(13)1


91.91 8.09

1.04 0.00 0.16 0.58


FETUS

7

MONTHS

(12)1


1.78


3.77

1.54 1.00


2.54


0.003 0.026 0.015 0.001


0.045


0.044 0.025 0.026 0.056


0.151


90.56 9.44

1.24 0.00 0.27 0.97


CHILD

1

MONTH

(14)2


2.48


3.98

1.77 1,21


2.98


0.005 0.028 0.018 0.002


0.053


0.054 0.009 0.028 0.062


0.153


86.15 13.85

2.40 0.27 0.06 2.26


4.99


5.43

2.37 1.06


3.43


0.001

0.022 0.005


0.094 0.019 0.035 0.083


0.231


CHILD

3

MONTHS

(20)


84.24 15.76

(4.07) 0.17 0.71 2.11


MONTHS

(21)'


7.06


6.40

1.35 0.95


2.30


0.014 0.037 0.011 0.002


0.064


0.172 0.011 0.019 0.068


0.270


82.71 17.29

2.89 0.40 0.94 3.41


7.65


7.01

1.64 1.00


2.64


0.019 0.047 0.016 0.002


0.084


0.131 0.011 0.029 0.074


0.245


ADULT

21 YEARS

(27)


73.60 70.34 26.40 29.66


ADULT

35

YEARS

(18)


ADUI/r

67

YEARS

(26)


6.03 (0.21) 1.97 7.52


15.73


8.29

1.44 0.94


2.38


0.039 0.069 0.002 0.004


0.114


0.273 0.011 0.017 0.083


0.384


4.69 1.36 2.49 9.43


17.97


8.90

1.71 1.10


2.81


0.050 0.062 0.007 0.005


0.124


0.231 0.015 0.055 0.059


0.360


76.26 23.74

7.33 2.33 1.78 2.83


14.27


7.60

0.95 0.93


1.88


0.036 0.069 0.009 0.002


0.116


0.317 0.011 0.035 0.058


0.421


1 See table 1.

2 Brain stem and cerebellum analyzed together, because of small sample.


476


C. G. MACARTHUR AND E. A. DOISY


TABLE 6 Brain stem: Weight of constituents in grams



FETtTS


FETUS


CHILD


CHILD


CHILD


ADULT


ADULT


ADULT



3 MONTHS


7 MONTHS


1 MONTH


3 MONTHS


8 MONTHS


21 YEARS


35 YEARS


67 YEARS



(13)>


(12)1


(14)2


(20)


(20)1


(21)


(18)


(26)


Brain


17.08


119.0


457.4


585.2


492.5


1122.4


1158.3


1297.9


Brain stem .


1.708


11.9


25.0


28.5


35.3


61.0


61.5


77.5


Water


1.57


10.77


21.54


24.00


29.20


44.90


43.26


59.10


Solids


0.138


1.125


3.46


4.50


6.10


16.10


18.24


18.40


Phospha









tids ....


0.0178


0.1476


0.600


1.160


1.024


3.678


2.884


5.681


Cerebro









sides . . .


0.0000


0.0000


0.068


0.048


0.141


0.128


0.836


1.806


Sulphatids


0.0027


0.0321


0.015


0.202


0.332


1.202


1.531


1.380


Choles









terol . . .


0.0099


0.1154


0.565


0.601


1.204


4.587


5.799


2.193


Total lipins.


0.0304


0.2951


1.248


2.012


2.700


9.595


11.052


11.059


Total pro









teins


0.0644


0.4736


1.358


1.814


2.475


5.057


5.474


5.890


Organic










extrac









tives... .


0.0263


0.2106


0.592


0.385


0.579


0.878


1.052


0.736


Inorganic










extrac









tives... .


0.0171


0.144


0.265


0.271


0.353


0.573


0.677


0.721


Total ex









tractives..


0.0434


0.3546


0.857


0.656


0.932


1.451


1.729


1.457


Lipin sul









phur


0.0001


0.0006


0.0003


0.0040


0.0138


0.0238


0.0308


0.0279


Protein










sulphur.


0.0004


0.0033



0.0105


0.0244


0.0421


0.0381


0.0535


Neutral










sulphur.


0.0003


0.0021


0.0055


0.0031


0.0007


0.0012


0.0043


0.0070


Inorganic










sulphur.


0.0000


0.0002


0.0013


0.0006


0.0014


0.0024


0.0031


0.0016


Total sul









phur


0.0008


0.0063



0.0182


0.0402


0.0695


0.0763


0.0900


CHEMICAL CHANGES IN HUMAN BRAIN


477


TABLE 6— Continued



FETUS 3 MONTHS

(13)'


FETUS

7 MONTHS

(12)1


CHILD 1 MONTH

(14)2


CHILD 3 MONTHS

(20)


CHILD

8 MONTHS

(21) J


ADULT 21 YEARS

(27)


ADULT 35 YEARS

(18)


ADULT 67 TEARS

(24)


Lipin

phosphorus..


0.0008


0.0064


0.0235


0.0490


0.0462


0.1665


0.1421


0.2457


Protein










phosphorus..


0.0004


0.0011


0.0048


0.0031


0.0039


0.0067


0.0092


0.0085


Organic










phosphorus..


0.0004


0.0033


0.0088


0.0054


0.0102


0.0104


0.0338


0.0271


Inorganic phosphorus..


0.0010


0.0074


0.0207


0.0194


0.0261


0.0506


0.0363


0.0450


Total phosphorus. . .


0.0026


0.0182


0.0578


0.0769


0.0865


0.2342


0.2214


0.3263


1 See table 1.

2 See table 4.


TABLE 7 Cerebellwn. Constituents in percentage of fresh tissue



FETUa 3 MONTHS

(12)1


FETUS 7 MONTHS

(12)1


CHILD 1 MOXTH

(14)2


CHILD 3 MONTHS

(17)


CHILD

S MONTHS

(1)'


ADULT 1 YEAR

(25)


ADULT 1 35 YEARS

(10)


ADULT 67 YEARS

(29)


Water


91.91 8.09

1.04 0.00 0,16 0.58


90.56 9.44

1.24 0.00 0.27 0.97


86.15 13.85

2.40

(0.27P (0.06)3 2.26


85.05 14.95

2.70 0.00 0.86 1.33


84.56 15.44

2.58 0.26 0.75 1.54


78.83 21.17

6.66 0.98 0.94 0.89


77.99 22.01

(2.84) 0.84 1.02 4.12


80.64


Solids


19.36


Phosphatids . . . Cerebrosides. . .

Sulphatids

Cholesterol ....


4.07 0.54 0.96 3.10


Total lipins


1.78


2.48


4.99


4.89


5.13


9.46


8.82


8.67


Total proteins . . .

Organic extractives

Inorganic extractives


3.77

1.54 1.00


3.98

1.77 1.21


5.43

2.37 1.06


6.97

1.90 1.19


6.94

2.10 1.28


8.95

1.55 1.23


8.60

(2.97) 1.61


7.66

1.68 1.36


Total extractives


2.54


2.98


3.43


3.09


3.38


2.78


(4.58)


3.04




Lipin sulphur. . Protein sulphur


0.003 0.026 0.015 0.001


0.005 0.028 0.018 0.002


0.001

0.022f 0.005


0.018 0.041 0.020 0.001


0.015 0.051 0.014 0.002


0.019 0.053 0.014 0.002


0.020 0.067 0.037 0.009


0.019 0.058


Neutral sulphur


0.006


Inorganic sulphur


0.002




Total sulphur


0.045


0.053



0.080


0.082


0.088


0.133


0.085


Lipin phosphorus

Protein phosphorus

Organic phosphorus

Inorganic phosphorus . .


0.044 0.025 0.026 0.056


0.054 0.009 0.028 0.062


0.094 0.019 0.035 0.083


0.122 0.045 0.020 0.075


0.115 0.046 0.039 0.086


0.278 0.042 0.022 0.110


0.140 0.036 0.080 0.114


0.178 0.028 (0.009) 0.106


Total phosphorus


0.151


0.153


0.231


0.262


0.286


0.452


0.370


0.321


1 See table 1.

2 See table 4.

' Earlier in the paper it was stated, that sulphur determinations were occasionally low. This is the case here. Because of the sugar content of sulphatids, if the latter is too low, these may be reported for cerebrosides when there are none free.

478


CHEMICAL CHANGES IN HUMAN BRAIN


479


TABLE 8

Cerebellum: Constituents in percentage of solids



FETUS

3

MONTHS

(13)'


FETUS

7

MONTHS

(12)1


CHILD

1 MONTH

(14) •i


CHILD

3

MONTHS

(17)


CHILD

8

MONTHS

(16)1


ADULT

21 YEARS

(25)


ADULT

35 YEARS

(10)


ADULT

67 YEARS

(29)


Phosphatids

Cerebrosides

Sulphatids


12.90 0.00 1.95 7.24


13.12 0.00

2.85 10.28


17.29

(1.95)3 (0.44)3 16.32


18.03 0.00 5.76

8.92


16.71 1.65 4.85 9.99


31.42 4.64 4.37 4.18


12.90 3.81 4.64

18.72


21.00

2.77 4 98


Cholesterol


16.05


Total lipins


22.09


26.25


36.00


32.71


33.20


44.61


40.07


44 70




Total proteins

Organic extractives . . . Inorganic extractives .


46.56

19.04 12.31


42.15

18.75 12.85


39.21

17.13 7.66


46.63

12.71 7.95


44.92

13.59 8.29


42.29

7.26

5.84


39.12

13.51 7.30


39.51

8.68 7.01


Total extractives


31.35


31.60


24.79


20.66


21.88


13.10


20.81


15.69


Lipin sulphur


0.039 0.314 0.187 0.013


0.051 0.294 0.183 0.022


0.009

0.158 0.036


0.115 0.273 0.129 0.009


0.097 0.323 0.092 0.015


0.088 0.252 0.064 0.007


0.093 0.307 0.168 0.044


100


Protein sulphur

Neutral Sulphur

Inorganic sulphur


0.296 0.032 0.009


Total sulphur


0.553


0.556



0.526


0.527


0.411


0.612


437




Lipin phosphorus

Protein phosphorus. . . Organic phosphorus. . . Inorganic phosphorus.


0.538 0.306 0.322 0.678


0.563 0.100 0.300 0.648


0.674 0.138 0.252 0.595


0.812 0.302 0.130 0.502


0.741 0.297 0.249 0.554


1.310 0.198 0.104 0.519


0.642 0.163 0.364 0.522


0.912 0.146 0.046 0.546


Total phosphorus


1.&44


1.611


1.659


1.746


1.841


2.131


1.691


1.650


1 See table 1.

2 See table 4. » See table 7.


480


C. G. MACARTHUR AND E. A. DOISY


TABLE 9 Cerebellimi: Weights of constituents in grams



FETUS


FETUS


CHILD


CHILD


CHILD


ADULT


ADULT


ADULT



3 MONTHS


7 MONTHS


1 MONTH


3 MONTHS


S MONTHS


21 TEARS


35 TEARS


67 TEARS



(13)'


(12)'


(14)2


(17)


(16)1


(25)


(10)


(29)


Brain


17.08


119.0


457.4


585.2


492.5


1122.4


1158.3


1297.9


Cerebellum .


1.708


11.9


37.4


42.6


48.2


111.4


110.8


145.4


Water


1.57


10.77


32.22


36.23


40.76


87.80


86.41


117.25


Solids


0.138


1.125


5.18


6.40


7.44


23.58


24.39


28.15


Phospha









tids


0.0178


0.1476


0.898


1.150


1.244


7.418


3.147


5.918


Cerebro









sides . . .


0.0000


0.000


0.101


0.000


0.125


1.091


0.931


0.785


Sulphatids


0.0027


0.0321


0.022


0.366


0.362


1.036


1.130


1.396


Choles









terol . . .


0.0099

0.1154


0.845


0.567


0.742


0.991


4.565


4.507


Total lipins.


0.0304


0.2951


1.866


2.084


2.473


10.536


9.772


12.606


Total pro









teins


0.0644


0.4736


2.031


2.969


3.345


9.968


9.529


11.138


Organic










extrac









tives . . .


0.0263


0.2106


0.886


0.810


1.012


1.704


3.291


2.443


Inorganic










extrac









tives... .


0.0171


0.144


0.397


0.507


0.617


1.370


1.784


1.977


Total ex









tractives..


0.0434


0.3546


1.283


1.317


1.629


3.074


5.075


4.420


Lipin sul









phur . . .


0.0001


0.0006


0.0004


0.0077


0.0072


0.0212


0.0222


0.0276


Protein










sulphur.


0.0004


0,0033



0.0175


0.0246


0.0590


0.0742


0.0843


Neutral










sulphur.


0.0003


0.0021


0.0082


0.0085


0.0067


0.0156


0.0410


0.0087


Inorganic










sulphur.


0.0000


0.0002


0.0019


0.0004


0.0010


0.0022


0.0100


0.0029


Total sul









phur


0.0008


0.0063



0.0341


0.0395


0.0980


0.1474


0.1236


1 See table 1.

2 See table 4.


TABLE 9— Continued



PETDS 3 MONTHS

(13)'


FETUS 9 MONTHS

(12)1


CHILD 1 MONTH

(14)2


CHILD 3 MONTHS

(17)


CHILD 8 MONTHS

(16)1


ADULT 21 YEARS

(25)


ADULT 35 YEARS

(10)


ADULT 67 YEARS

(29)


Lipin phosphorus .


0.0008


0.0064


0.0352


0.0520


0.0554


0.3097


0.1551


0.2588


Protein










phosphorus .


0.0004


0.0011


0,0071


0.0192


0.0222


0.0468


0.0399


0.0407


Organic phosphorus .


g.ooo4


0.0033


0.0131


0.0085


0.0188


0.0245


0.0886


0.0131


Inorganic phosphorus .


0.0010 0.0026


0.0074


0.0311


0.0320


0.0415


0.1225


0.1263


0.1541


Total phosphorus . . .


0.0182


0.08&4


0.1116


0.1378


0.5035


0.4100


0.4667


TABLE 10 Whole brain: Constituents in percentage of fresh tissue



FETUS

3

MONTHS


FETUS

7

MONTHS


CHILD

1 MONTH


CHILD

3

MONTHS


CHILD

8

MONTHS


ADULT

21 YEARS


ADULT

35 YEARS


ADULT

67 YEARS


Water

Solids


91.91 8.09


90.56 9.44


87.81

12.19


86.75 13.25


85.47 14.53


77.25 22.75


73.20 26.80


78.58 21.42


Phosphatids

Cerebrosides

Sulphatids


1.04

0.00

.16

.58


1.24

0.00

.27

.97


2.00 .04 .22

1.63


1.92 .27 .53

1.68


3.09 .46 .56

1.15


5.80 1.20 1.75 3.57


6.35 2.35 1.69 4.36


6.30 1.62 1.33


Cholesterol


2.62


Totallipins


1.78


2.48


3.89


4.42


5.26


12.32


14.75


11.87




Total proteins


3.77

1.54 1.00


3.98

1.77 1.21


4.69

2.43 1.18


5.47

2.29 1.08


6.24

1.99 1.05


8.14

1.24 1.04


8.95

2.10 0.99


7.54


Organic extractives

Inorganic extractives . . .


0.98 1.01


Total extractives


2.54


2.98


3.61


3.37


3.04


2.28


3.09


1.99




Lipin sulphur


0.003 0.026 0.015 0.001


0.005 0.028 0.018 0.002


0.004 0.029 0.022 0.004


0.011 0.038 0.026 0.005


0.012 0.066 0.016 0.010


0.035 0.054 0.013 0.002


0.034 0.043 0.023 0.009


0.026


Protein sulphur


0.061


Neutral sulphur

Inorganic sulphur


0.014 0.003


Total sulphur


0.045


0.053


0.059


0.080


0.104


0.104


0.109


0.104




Lipin phosphorus

Protein phosphorus

Organic phosphorus

Inorganic phosphorus. . .


0.044 0.025 0.026 0.056


0.054 0.009 0.028 0.062


0.081 0.007 0.035 0.082


0.086 0.009 0.051 0.074


0.124 0.012 0.032 0.060


0.259 0.016 0.013 0.064


0.280 0.016 0.052 0.055


0.248 0.014 0.010 0.059


Total phosphorus


0.151


0.153


0.205


0.220


0.228


0.352


0.403


0.331




TABLE 11 Whole brain: Constituents in percentage of solids


FETUS

3

MONTHS


Phosphatids

Cerebrosides

Sulphatids

Cholesterol

Total lipins

Total proteins

Organic extractives

Inorganic extractives . . .

Total extractives

Lipin sulphur

Protein sulphur

Neutral sulphur

Inorganic sulphur

Total sulphur

Lipin phosphorus

Protein phosphorus

Organic phosphorus

Inorganic phosphorus. . .

Total phosphorus


22.09


12.90 0.00 1.95 7.24


26.25


46.56

19.04 12.31


42.15

18.75 12.85


31.35


0.039 0,314 0.187 0.013


0.553


0.538 0.306 0.322 0.678


1.844


FETUS

7

MONTHS


13.12

0.00

2.85

10.28


31.90


38.46

19.93 9.68


31.60


0.057 0.294 0.183 0.022


0.556


0.563 0.100 0.300 0.648


CHILD 1

MONTH


16.40 0.33 1.80

13.37


33.30


41.30

17.29 8.15


29.61


0.033 0.238 0.180 0.033


0.184


0.664 0.057 0.287 0.672


1.611


1.680


CHILD 3

MONTHS


14.50 2.04 4.00

12.76


21.26 3.16 3.85 7.91


36.19


42.93

13.69

7.22


25.44


0.083 0.287 0.196 0.038


0.604


0.649 0.068 0.385 0.559


1.661


CHILD

8

MONTHS


25.52 5.28 7.70

15.70


54.20


35.82

5.46 4.58


20.91


0.083 0.454 0.110 0.068


0.715


0.853 0.083 0.220 0.413


1.569


ADULT

21 YEARS


23.69 8.77 6.30

16.26


55.01


33.38

7.83 3.69


10.04


0.154 0.238 0.057 0.009


0.458


1.140 0.070 0.057 0.282


1.549


ADULT

35

YEARS


29.42 7.56 6.21

12.24


55.43


11.52


0.127 0.160 0.086 0.034


0.407


1.044 0.060 0.194 0.205


1.503


ADULT

67 TEARS


35.21

4.58 4.72


9.30

0.121 0.285 0.065 0.014

0.485

1.158 0.065 0.047 0.276

1.546


CHEMICAL CHANGES IN HUMAN BRAIN


483


TABLE 12 Whole brain: Weights of constituents in grams



FETUS

3

MONTHS


FETUS


CHILD


CHILD


CHILD


ADULT


ADULT


ADULT



7 MONTHS


1 MONTH


3 MONTHS


8 MONTHS


21 YEARS


35 YEARS


67 YEARS


Whole brain


17.08


119.0


457.4


585.2


492.5


1122.4


1158.3


1297.9


Water


15.70


107.7


401.7


507.5


421.0


867.2


848.0


1020.0


Solids


1.38


11.25


55.74


77.58


71.54


255.2


310.3


278.0


Phospha









tids ....


0.178


1.476


9.158


11.250


15.228


65.05


73.67


81.93


Cerebro









sides . . .


0.000


0.000


0.169


1.590


2.266


13.479


27.207


21.081


Sulpha









tids ....


0.027


0.321


1.017


3.138


2.744


19.718


19.621


17.296


Choles









terol . . .


0.099


1.154


7.453


9.906


5.666


40.058


50.604


34.120


Total lipins.


0.304


2.951


17.774


25.896


25.863


138.23


171.02


154.27


Total pro









teins


0.644


4.736


21.439


31.973


30.730


91.305


103.65


98.00


Organic










extrac









tives . . .


0.263


2.106


11.116


13.435


9.811


13.892


24.363


12.639


Inorganic










extrac









tives . . .


0.171


1.440


5.362


6.228


5.180


11.633


11.431


13.018


Total ex









tractives..


0.434


3.546


16.478


19.663


14.991


25.525


35.794


25.657


Lipin










sulphur.


0.0005


0.0060


0.0207


0.0627


0.0620


0.3870


0.3880


0.3453


Protein










sulphur.


0.0044


0.0333


0.1300


0.2230


0.3310


0.6051


0.4973


0.7938


Neutral










sulphur.


0.0026


0.0214


0.1007


0.1456


0.0814


0.1398


0.2623


0.1767


Inorganic










sulphur.


0.0002


0.0024


0.0192


0.0270


0.0514


0.0236


0.1011


0.0365


Total sul









phur.. .. . .


0.0077


0.0631


0.2706


0.4583


0.5248


1 . 1555


1.2487


1.3525


484


C. G. MACAETHUR AND E. A. DOISY


TABLE \2— Continued



FETUS

3

MONTHS


FETUS

7

MONTHS


CHILD 1

MONTH


CHILD 3

MONTHS


CHILD

8

MONTHS


ADULT

21

TEARS


ADULT

35 TEARS


ADULT

67 TEARS


Lipin phosphorus .


0.0075


0.0643


0.3747


0.5020


0.6206


2.0980


3.2550


3.2360


Protein










phosphorus .


0.0043


0.0102


0.0319


0.0533


0.0591


0.1775


0.1871


0.1782


Organic phosphorus .


0.0044


0.0333


0.1639


0.2969


0.1600


0.1489


0.6054


0.1262


Inorganic phosphorus .


0.0096


0.0738


0.3758


0.5415


0.2926


0.7241


0.6356


0.7691


Total phosphorus . . .


0.0258


0.1821


0.9463


1.2836


1.1323


3.9585


4.6831


4.3095


Figure 1 was plotted from the data in this table relating to the earlier period of growth.


CHEMICAL CHANGES IN HUMAN BRAIN


485


TABLE 13 Whole brain: Milligrams added per day



UP TO 3-MONTH

FETUS


3-MONTH

TO

7-MONTH

FETUS


7-MONTH

FETUS TO

1-MONTH

CHILD


1-MONTH

TO

3-MONTH

CHILD


3-MONTH

TO

8-MONTH

CHILD


8-MONTH

TO 21-YEAR


Whole brain

Water


190.0

174.0 15.3

1.98 0.0 0.30 1.10


848.0

766.0

82.3

10.80 0.0 2.45

8.79


3764.0

3270.0 494.0

85.3 1.88 7.73 70.0


2127.0

1763.0 364.0

34.9 23.7 35.4 40.9


501.6

417.0 84.6

26.3 4.07 2.99 0.74


131.2 113


Solids


18 2


Phosphatids


5.4


Cerebrosides


1.4


Sulphatids


2 2


Cholesterol


4 4




Total lipins


3.38


22.04


164.9


135.1


33.9


13 4




Total proteins


7.16

2.81 1.90


34.1

15.4 10.6


185.6

100.1 43.6


175.6

38.7 14.4


38.5

7.2 5.2


5 1


Organic extractives

Inorganic extractives ....


-0.6 -0.3


Total extractives


4.81


26.0


143.7


53.1


11.4


-0.3


Lipin sulphur


0.006 0.049 0.029 0.002


0.05 0.24 0.16 0.02


0.16 1.07 0.88 0.19


0.70 1.55 0.75 0.13


0.08 0.61 0.01 0.11


0.04


Neutral sulphur

Inorganic sulphur


0.0 -0.01


Total sulphur


0.086


0.47


2.30


3.13


0.81


0.03




Lipin phosphorus

Protein phosphorus

Organic phosphorus

Inorganic phosphorus. . . .


0.083 0.048 0.049 0.107


0.47 0.081 0.24 0.54


3.45 0.24 1.45 3.36


2.12 0.36 2.22 0.93


1.01 0.09 0.0 0.17


0.27

0.01

-0.02

0.03


Total phosphorus


0.287


1.30


8.50


5.62


1.27


0.29


A part of these data are plotted in graph 2.


TABLE 14 Whole brain: Average percentage increase per day


Whole brain

Water

Solids

Phosphatids

Cerebrosides

Sulphatids

Cholesterol

Total lipins

Proteins

Organic extractives. . Inorganic extractives Total extractives


3-MONTH

FETUS


7-MONTH

FETUS


1-MONTH


3-MONTH


2.3


1.7


0.88


0.26


2.1


1.7


0.88


0.23


2.4


1.7


1.0


0.36


2.3


1.8


0.79


0.36


0.0


0.0


4.7


1.6


2.7


1.9


1.3


1.1


2.5


1.8


1.1


0.1


2.2 •


1.8


1.3


0.32


2.3


1.6


1.1


0.5


2.3


1.7


0.42


0.13


2.2


1.6


0.56


0.26


2.3


1.7


0.6


0.15


8-MONTH

0.028

0.04

0.046

0.03

0.057

0.072

0.02

0.03

0.02

0.00

0.00

0.00


These data were estimated from curves similar to, but larger than curves (1). These were plotted from data in table 10.

In the calculation from the curves a period of one-half month before and onehalf month after each age was used. It is believed that the enormous figures for rate of growth sometimes presented for early fetal life are due to the method of calculating from the weight at the beginning of the period. When the growth rate is changing rapidly, the error in such calculations is very large.

The curves in graph 3, excepting extractives (c), are plotted from this table,

TABLE 15 Whole brain: Average percentage increase per day

8 MONTH21 YEARS


Whole brain

Water

Solids

Phosphatids

Cerebrosides

Sulphatids

Cholesterol

Total lipins

Proteins

Organic extractives. . . Inorganic extractives. Total extractives


3-7

MONTH FETUS


7 MONTH

FETUS 1 MONTH


1 MONTH3 MONTH


3 MONTH8 MONTH


1.25


1.31


0.41


0.067


1.24


1.28


0.39


0.065


1.30


1.47


0.55


0.081


1.31


1.59


0.34


0.13


0.00


(2.23)


2.69


0.14


1.41


1.16


1.70


0.075


1.46


1.63


o;47


0.073


1.36


1.59


0.62


0.093


1.27


1.42


0.66


0.087


1.28


1.52


0.32


0.046


1.32


1.28


0.25


0.067


1.30


1.44


0.29


0.048


0.013

0.014

0.01

0.012

0.016

0.018

0.018

0.014

0.007

0.0

0.0

0.0


Calculated from data in table 11. The average number of milligrams added per day was divided by the average weight for the given period, instead of the weight at the beginning of the period, as is usually done. When there are rapid changes in weight, this method is not as accurate as that used in table 12. It is believed that the temporary rise in growth at about the seventh month of fetal life is due to the method of calculation.

The curve marked extractives (c) in graph 3 was plotted from the above data.

486


SUBJECT AND AUTHOR INDEX


ACTIVITY of the nervous system. III. On the amount of non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic 397

Albino mouse. The nervus facialis of the. .. . 81

rat in Miiller's fluid. Factors influencing the behavior of the brain of the. ..411

rats during twenty-four hovirs after

feeding. Metabolic activity of the nervous system. III. On the amount of non-protein nitrogen in the brain of 397

Allen, William F. Application of the March! method to the study of the radix mesencephalica trigemini in the guineapig 169

Allis, Edw.\rd Phelps, Jr. The ophthalmic nerves of the gnathostome fishes 69

Arey, Leslie B. A retinal mechanism of efficient vision 343

Ayers, Howard. Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the ' nose' 323

BEHAVIOR of the brain of the albino rat in Miiller's fluid. Factors influencing

the 411

Brain during growth. Quantitative chemical

changes in the human 445

of albino rats during twenty-four hours

after feeding. Metabolic activity of the" nervous system. HI. On the amount of

non-protein nitrogen in the 397

of the albino rat in Miiller's fluid. Factors influencing the behavior of the 411

CELLS in normal, subnormal, and senescent human cerebella, with some notes on functional localization. A preliminary quantitative study of the Purkinje. 229

tunnel space, and Nuel's spaces in the

organ of Corti. The development of the pillar 283

Cell with especial consideration of the ' Golginet' of Bethe, nervous terminal feet and the 'nervous pericellular terminal net' of Held. On the finer structure of the synapse of the Mauthner 127

Cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the 'nose.' Vertebrate 323

Cerebella, with some notes on functional localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human 229

Changes in the human brain during growth. Quantitative chemical 445

Chemical changes in the human brain during growth. Quantitative 445

Corti. The development of the pillar cells, tunnel space, and Nuel's spaces in the organ of 283

DEVELOPMENT of the pillar cells, tunnel space, and Nuel's spaces in the

organ of Corti. The 283

DoiSY, E. A., Mac.;\rthur,C. G.,and. Quantitative chemical changes in the human brain during growth 445

487


EFFICIENT vision. A retinal mechanism of 343

Ellis, .Roiiert S. A preliminary quantitative .study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional localization 229

FACIALIS of the albino mouse. The nervus 81

Factors influencing the behavior of the brain of the albino rat in Miiller's fluid 411

Fiber in teleosts. Concerning Reissner's 217

Fishes. The ophthalmic nerves of the gnathostome 69

Fluid. Factors influencing the behavior of the brain of the albino rat in Miiller's. ... 411

Formation of the 'nose.' Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the. . 323

Functional localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on 229

GNATHOSTOME fishes. The ophthalmic nerves of the 69

Golgi. Frontispiece. Portrait of Professor Camillo 168

'Golgi-net' of Bethe, nervous terminal feet and the ' nervous pericellular terminal net' of Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 127

Growth. Quantitative chemical changes in the human brain during 445

Guinea-pig. Application of the Marchi method to the study of the radix mesencephalica trigemini in the 169

HEAD, resulting in the formation of the 'nose.' Vertebrate cephalogenesis. IV. Transformation of the anterior end of

the 323

Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the ' Golgi-net' of Bethe, nervous terminal feet and the 'nervous

pericellular terminal net' of 127

Human cerebella, with some notes on functional localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent 229

JORDAN, HovEY. Concerning Reissner's fiber in teleosts 217

KOMINE, Shigeyuki. Metabolic activity of the nervous system. III. On the amount of non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding 397

LARSELL, Olof. Studies on the nervus terminalis: Mammals 1

• Studies on the nervus terminalis:

turtle 423


488


INDEX


Localization. A preliminary quantitative study of the Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional 229

MACARTHUR, C. G., and DoieY, E. A. Quantitative chemical changes in the human brain during growth 445

Mammals. Studies on the nervus terminalis. 1

Marchi method to the study of the radix mescncephalica trigemini in the guinea-pig. Application of the 169

MjVRCI, Kitoy.\su. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 'Golgi-net' of Bethe, nervous terminal feet and the ■ nervous pericellular terminal net' of Held. 127

. The effect of over-activity on the morphological structure of the synapse. 253

Mauthner cell with especial consideration of the * Golgi-net' of Bethe, nervous terminal feet and the ' nervous pericellular terminal net' of Held. On the further structure of the synapse of the 127

Mesencephalica trigemini in the guinea-pig. Application of the Marchi method to the study of the radix 169

Metabolic activity of the nervous systern. III. On the amount of non-protein nitrogen in the brain of albino rats during twentj'-four hours after feeding 397

Morphological structure of the synapse. The effect of over-activity on the 253

Mouse. The nervus facialis of the albino 81

Miiller's fluid. Factors influencing the behavior of the brain of the albino rat in. . . 411

NERVES of the gnathostome fishes. The ophthalmic 69

Nervous system. III. On the amount of nonprotein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the 397

— terminal feet and the 'nervous pericellular terminal net' of Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 'Golgi-net' of Bethe 127

Nervus facialis of the albino mouse. The.... 81

terminalis: Mammals. Studies on the 1

turtle. Studies on the 423

Net' of Held. On the finer structure of the synapse of the Mauthner cell with especial consideration of the 'Golgi-net' of Bethe, nervous terminal feet and the ' nervous pericellular terminal 127

Nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the nervous system. III. On the amount of non-protein 397

Non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the nervous system. III. On the amount of 397

' Nose.' Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the . . 323

Nuel's spaces in the organ of Corti. The development of the pillar cells, tunnel space, and 283

OGATA, D., and Vincent, Swale. A contribution to the study of vasomotor

reflexes 355

Ophthalmic nerves of the gnathostome fishes .

The 69

Organ of Corti. The development of the pillar cells, tunnel space, and Nuel's

spaces in the. 283

Over-activity on the morphological structure of the synapse. The effect of 253


PILLAR cells, tunnel space, and Nuel's spaces in the organ of Corti. The development of the 283

Pl.^nt, J.\mes Stu.\rt. Factors influencing the behavior of the brain of the albino

rat in Miiller's fluid 411

Purkinje cells in normal, subnormal, and senescent human cerebella, with some notes on functional localization. A preliminary quantitative study of the 229

RADIX mesencephalica trigemini in the guinea-pig. Application of the Marchi

method to the study of the 169

Rat in Miiller's fluid. Factors influencing the

behavior of the brain of the albino 411

Rats during twenty-four hours after feeding. » Metabolic activity of the nervous systeni. S III. On the amount of non-protein ni trogen in the brain of albino 397

Reflexes. A contribution to the study of

vasomotor 355

Reissner's fiber in teleosts. Concerning 217

Retinal mechanism of efficient viaion. A 343

Rhinehart, D. a. The nervous facialis of the albino mouse 81

SPACE, and Neul's spaces in the organ of Corti. The development of the pillar cells, tunnel 283

Spaces in the organ of Corti. The development of the pillar cells, tunnel space, and Nuel's 283

Structure of the synapse of the Mauthner cell with especial consideration of the ' Golginet' of Bethe, nervous terminal feet and the ' nervous pericellular terminal net' of Held. On the finer 127

Structure of the synapse. The effect of overactivity on the morphological 253

Synapse of the Mauthner cell with especial

consideration of the ' Golgi-net' of Bethe,

• nervous terminal feet and the 'nervous

pericellular terminal net' of Held. On

the finer structure of the 127

The effect of over-activity on the morphological structure of the 253

System. III. On the amount of non-protein nitrogen in the brain of albino rats during twenty-four hours after feeding. Metabolic activity of the nervous 397

TELEOSTS. Concerning Reissner's fiber in 217

Terminalis: Mammals. Studies on the nervus 1

turtle. Studies on the nervus 423

Terminal net' of Held. On the finer structure of the synapse of the Mauthner cell with especial corisideration of the 'Golginet' of Bethe, nervous terminal feet and the ' nervous pericelhJar 127

Transformation of the anterior end of the head, resulting in the formation of the 'nose.' Vertebrate cephalogenesis. IV.. 323

Trigemini in the guinea-pig. Application of the Marchi method to the study of the radix mesencephalica 169

Tunnelspace.and Nuel'sspacesin theorganof Corti. The development of the pillar cells 283

Turtle. Studies on the nervus terminalis. . . 423

VAN DER STRICHT, O. The development of the pillar cells, tunnel space, and Nuel's spaces in the organ of Corti. 283 Vasomotor reflexes. A contribution to the study of 3.55

Vertebrate cephalogenesis. IV. Transformation of the anterior end of the head, resulting in the formation of the 'nose'; . . . 323 Vincent, Swale, Ogata, D., and. A contribution to the study of vasomotor reflexes. 355 Vision. A retinal mechanism of efficient 343


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