Difference between revisions of "2014 Group Project 7"

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'''1858''' – Joseph von Gerlach brings forth a new process to differentiate between the different microstructures in the brain by treating the sample to a solution of ‘Carmine’. This solution made the sample no longer appear homogenous under the lens but able to be differentiable to its components
 
'''1858''' – Joseph von Gerlach brings forth a new process to differentiate between the different microstructures in the brain by treating the sample to a solution of ‘Carmine’. This solution made the sample no longer appear homogenous under the lens but able to be differentiable to its components
  
'''1889''' – Camille Golgi comes forth with the procedure of impregnating hardened brain tissues with silver nitrate solution which resulted in the staining of nerve cells. Possibility to trace cellular prolongations definitely to their termini now present
+
'''1889''' – Camille Golgi comes forth with the procedure of impregnating hardened brain tissues with silver nitrate solution which resulted in the staining of nerve cells. Possibility to trace cellular prolongations definitely to their termini now present. Ramon y Cajal announces his discoveries. Old theory of union of nerve cells into an endless mesh-work is discarded altogether, the new theory of isolated nerve elements ‘theory of neurons’ is fully established in its place <Ref><Pubmed>17490748</pubmed></ref>
 
 
'''1889''' – Ramon y Cajal announces his discoveries. Old theory of union of nerve cells into an endless mesh-work is discarded altogether, the new theory of isolated nerve elements ‘theory of neurons’ is fully established in its place  
 
  
 
==Current research models and findings==
 
==Current research models and findings==

Revision as of 02:30, 20 October 2014

2014 Student Projects
2014 Student Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8
The Group assessment for 2014 will be an online project on Fetal Development of a specific System.

This page is an undergraduate science embryology student and may contain inaccuracies in either description or acknowledgements.

Neural - CNS

Introduction

The Central Nervous System (CNS) is a complex network of neurons which are responsible for the sending, recieving and integration of information from all parts of the body, serving as the processing center of the bodies nervous system. The CNS controls all bodily functions (sensory and motor), consisting of 2 main organs; The Brain and Spinal Cord

Brain

The Brain is the body's control center consisting of 3 main components; Forebrain, Midbrain and Hindbrain. The forebrain functions in receiving and processing sensory information, thinking, perception, and control of motor functions as well as containing essential structures; Hypothalamus and Thalamus, which are responsible in motor control, autonomic function control and the relaying of sensory information. The Midbrain along with the Hindbrain together form the brain-stem and are both important in auditory and visual responses

Spinal Cord

The Spinal Cord is a cylindrical shaped structure composes of nerve fiber bundles which is connected to the brain via the brain-stalk formed from the Midbrain and Hindbrain, running through the spinal canal in the vertebrae (in animals) from the neck to the lower back. The spinal cord plays the important role of transmitting information from bodily organs and external stimuli to the brain and acts as a channel to send important signals to other parts of the body. The nerve bundles in the Spinal cord are divided into

1) Ascending bundles - Transmits Sensory information from the body to the brain

2) Descending bundle - Transmits Motor function information from the brain to the body

Before fetal period, nerulation occurs that ectoderm forms initial structure of the CNS and folds upon itself to form neural tube towards the end of week 3. The head portion becomes the brain, which further differentiates into forebrain, midbrain and hindbrain, while the middle portion becomes the brain stem. Around week 5, neural tube differentiates into the proencephalon (forebrain), the mesencephalon (midbrain) and the rhombencephalon (hindbrain). By week 7, the prosencephalon divides into the telencephalon and the diencephalon, while the rhombencephalon divides into the metencephalon and the myelencephalon. The formation of these 2 additional structures creates 5 primary units that will become the mature brain.

In this website, CNS development during the fetal period, the current research models and finding, historic findings and abnormalities that can occur in the fetal period is identified.

Development during fetal period

Neural-development.jpg

Timeline of human neural development [1]

1. cell proliferation

  • Formation of neurons and glia
  • Begins around 40th embryonic day and is almost complete around the 6th month of gestation [2]
  • Occurs in germinal matrix that comprised of ventricular and subventricular proliferative zones of cells
  • Ventricular zone: pseudostratified columnar epithelium, it is the only proliferative zone in some parts of the developing CNS
  • Subventricular zone: for example, form neurons of major subdivisions of hippocampus [3].

Somatosensory cortex of E20 rat.jpeg

Image of coronal sections of somatosensory cortex of E20 rat showing boundaries between the ventricular zone (VZ), inner subventricular zone (iSVZ) and outer SVZ (oSVZ) through staining [4]

2. cell migration

  • migration of cells from the 2 ventricular zones to their final positions
  • 2 migrations
  1. primary migration: occurs from week 8 to 16 of gestation, and continues to week 25 with lesser activity
  2. passive migration: result in the oldest cells locating farthest from the proliferative zone as they are pushed away by recently generated cells, this lead to midline structures including thalamus and regions of the brain stem


Internurons migration in cerebral cortex.jpg

Image of interneurons migration and interactions with radial glia in the developing cerebral cortex [5]

3. cell differentiation

  • begins after the migration of neuronal and glial cells to the final positions
  • starts about the 25th month of gestation until adolescence
  • axonal and dendritic properties become fine-tuned as cells transform into committed members of specialized systems

4. cell death (apoptosis)

  • 2 mechanisms: axonal retraction and neuronal pruning [6]
  • Axonal retraction: recession of the collaterals of a neuron’s axon or shrinking of the terminal arborization of the axon
  • Other connections are removed through selective cell death in which neurons die as a result of failing to establish appropriate connections
  • Critical for appropriate brain development


Brain Development

- The human brain development begins in the 3rd gestational week with the start marked by differentiation of the neural progenitor cells

- By the end of the embryonic period in gestation week 9 (GW9), the basic structures of the brain and CNS are established as well as the major parts of the Central and Peripheral nervous systems being defined

- The early fetal period (mid-gestation) is a critical period in the development of the neocortex, as well as the formation of vital cortical neurons which are vital in the brain processing information

During Fetal Period

- Extends from the ninth gestational weeks through to the end of gestation

- Gross morphology of the developing brain undergoes striking change during this time, beginning as a smooth structure and gradually developing the characteristic mature pattern of gyral and sulcal folding

- Brain development begins rostral in GW8, proceeding caudally until it is complete at GW22

- Secondary sulci emerge between GW30-35

- Formation of Tertiary sulci begins during GW36 and into the postnatal period

- Different population of neurons form grey matter structures in many regions of the brain including hindbrain and spinal column, cerebellum, midbrain structure and the neocortex

- Neurons, after production, migrate away from the proliferative regions of the VZ, the neurons that will form the neocortex migrate in an orderly fashion forming the 6 layered neocortical mantle

- The major fibre pathways make up the brain white matter

- AS development proceeds, the brain becomes larger and the primary mode of neuronal migration from the VZ changes.


Increase in size and weight

Brain ventricles and ganglia development 03.jpg

Image of brain and ventricular development [7]

Brain fissure development 02.jpg

Image of brain fissure development [8]

sulcation and gyration

Sulcation: development of sulci. Primary sulci appear as shallow grooves on the surface of the brain and become more deeply infolded. Secondary sulci are formed from the development of side branches of primary sulci [9]

Gyration: development of gyrus that occurs late during fetal development until end of the pregnancy or even later after birth [10]


Weeks Visible anatomical details
20-21 smooth, "lissencephalic" brain, wide Sylvian fissures
22-23 corpus callosum; beginning of calcarine and hippocampal fissures and of callosal sulci
24-25 start of opercularization of Sylvian fissures; calcarine fissures and cingular sulci
26 central and collateral sulci
27 marginal and precentral sulci
28 postcentral and intraparietal sulci
29 inferior frontal sulci; bright white matter, dark cortical ribbon
30-31 narrower ventricular system and subarachnoid spaces
32 superior and inferior temporal sulci
33 external occipitotemporal sulci
34-35 close to final shape of gyration
36-37 completed opercularization of Sylvian fissures; narrow pericerebral fluid spaces; dark subcortical fibres and corona radiata
38-40 dark posterior limbs of internal capsules

table obtained from <pubmed>20608424</pubmed> [11]

Spinal Cord Development

The spinal cord is formed from parts of the neural tube during embryonic and fetal development

Meninges Development

Historical Research and Findings

Historical knowledge, predating when modern research techniques were made available, in understanding and studying the Central Nervous structure of humans and other animals were gathered by various investigations by Pathologists, Anatomists, Physiologists from the early 1800’s.

1824 – Luigi Rolando first discovered a method to study Central Nervous system structures via cutting chemically hardened pieces of brain tissue into thin sections for microscopical observations.

1842 - Rolando’s method of observing CNS structures was perfected by Benedikt Stilling by cutting series of consecutive slices of the same tissue, this allowed the ability to trace nerve tracts and establish spacial relations

1833 – Robert Remak discovers that the brain tissue is cellular. Ehrenberg discovers that it is also fibrillar

1858 – Joseph von Gerlach brings forth a new process to differentiate between the different microstructures in the brain by treating the sample to a solution of ‘Carmine’. This solution made the sample no longer appear homogenous under the lens but able to be differentiable to its components

1889 – Camille Golgi comes forth with the procedure of impregnating hardened brain tissues with silver nitrate solution which resulted in the staining of nerve cells. Possibility to trace cellular prolongations definitely to their termini now present. Ramon y Cajal announces his discoveries. Old theory of union of nerve cells into an endless mesh-work is discarded altogether, the new theory of isolated nerve elements ‘theory of neurons’ is fully established in its place [12]

Current research models and findings

<pubmed>19786578</pubmed> <pubmed>21501576</pubmed> <pubmed>21492152</pubmed> <pubmed>24664314</pubmed> <pubmed>24639464</pubmed> <pubmed>24284205</pubmed> <pubmed>24177053</pubmed> <pubmed>24051984</pubmed> <pubmed>24996922</pubmed>


Current Research

Most previous studies describe overall growth of brain based upon in utero imaging studies with the use of magnetic resonance imaging (MRI) and ultrasound; however, complicated folding of the cortex in adult brain is due to different rates of regional tissue growth. In the following study, maps of local variation in tissue expansion are created for the first time in the living fetal human brain, in order to examine how structural complexity emerges in fetal brain.

Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero [13]


Recent development in fetal MRI motion correction and computational image analysis techniques were employed in this study to help with the understanding of the patterns of local tissue growth. These techniques were applied to 40 normal fetal human brains in the period of primary sulcal formation (20–28 gestational weeks). This time period covers a developmental stage from the point at which only few primary sulci have developed until the time at which most of the primary sulci have formed, but before the emergence of secondary sulci on MRI. This developmental period is also important clinically, since the clinical MRI scans are also performed at this gestational age. Therefore it is important to describe the normal growth patterns in this period in order to be able to recognise abnormalities in the formation of sulci and gyri.

Techniques mentioned previously were utilised to quantify tissue locations in order to map the tissues that were expanding with a higher or lower growth rate than the overall cerebral growth rate. It was found that relatively higher growth rates were detected in the formation of precentral and postcentral gyri, right superior temporal gyrus, and opercula whereas slower growth rates were found in the germinal matrix and ventricles. Additionally, analysis of the cortex illustrated greater volume increases in parietal and occipital regions compared to the frontal lobe. It was also found that gyrification was more active after 24 gestational weeks. These maps of the fetal brain were used to create a three-dimensional model of developmental biomarkers with which abnormal development in human brain can be compared.


The following are recent studies that use a similar model to what was described above:

Mapping Longitudinal Hemispheric Structural Asymmetries of the Human Cerebral Cortex From Birth to 2 Years of Age [14]

  • In this study longitudinal cortical hemispheric asymmetries were mapped in infants using surface-based morphometry of magnetic resonance images
  • Some of the findings of this study:

-Sexual dimorphisms of cortical asymmetries are present at birth with males having larger sizes of asymmetries.

-The left supra marginal gyrus is much more posterior compared to the right supra marginal gyrus at birth and this position difference increases for both males and females by 2 years of age.

-The right superior temporal parieto-occipital sulci are significantly larger and deeper than those in the left hemisphere while the left planum temporale is significantly larger and deeper than that in the right hemisphere at all 3 ages.

  • It was concluded in this study that early hemispheric structural asymmetries are inherent and gender related.


Sexually Dimorphic White Matter Geometry Abnormalities in Adolescent Onset Schizophrenia [15]

  • In this study, they investigate the geometry of inter-hemispheric white matter connections in patients with schizophrenia with a particular focus on sexual differences in white matter connection.
  • They find a correlation between the sex-dependent abnormality in the geometry of white matter connecting the two hemispheres and the severity of schizophrenia


Asymmetry of White Matter Pathways in Developing Human Brains [16]

Cortical Overgrowth in Fetuses With Isolated Ventriculomegaly [17]

Future Research

Abnormalities

Microcephaly, Macrocephaly and Hydrocephalus

Microcephaly and macrocephaly refer to abnormal head size. These abnormalities are seen in less than 2% of all newborns. Learning abnormalities and neurophysiological malfunctioning associated with these abnormalities are dependent on etiology, severity and patient’s age. The most frequent cause of macrocephaly is hydrocephalus.

Microcephaly

  • Noticeable reduction in the size of brain is observed due to factors that kill the dividing cells in the ventricular germinal zone. These dividing cells give rise to brain cells (both neurons and glia).
  • Microcephaly is specifically defined as a head size more than two standard deviations below the mean for age, gender and race.There are two diagnostic types of primary and secondary microcephaly.
  • Primary Microcephaly: Abnormal development is observed in the first seven months of gestation.
  • Secondary Microcephaly: Abnormal development occurs during the last 2 months of gestation (prenatal period) in the secondary type.
  • Microcephaly is caused by various factors that prevent normal proliferation and migration of cells during CNS development. These factors are divided into physical (irradiation, raised maternal temperature), chemical (anticancer drugs) and biological (infection of uterus due to rubella, cytomegalovirus and herpes simplex virus).
  • Genetic defects and chromosomal disorders can also play a role.All of these factors result in destruction of the brain tissue (encephalopathy) with multiple areas of scarring and cyst formation.

Occipital encephalocele associated with microcephaly.jpg

Clinical photograph showing the giant occipital encephalocele associated with microcephaly and micrognathia[18]


Macrocephaly

  • In patients with macrocephaly the head is enlarged.
  • Macrocephaly is specifically defined as a head size more than two standard deviations above the mean for age, gender and race.
  • Macrocephaly is a syndrome of diverse etiologies rather than a disease and the most frequent cause is hydrocephalus.

Hydrocephalus

  • Progressive enlargement of head due to accumulation of cerebrospinal fluid in ventricles is known as hydrocephalus.
  • Excessive accumulation of cerebrospinal fluid is due to an imbalance between the formation and absorption of cerebrospinal fluid (communicating hydrocephalus) or obstruction of circulation of cerebrospinal fluid (non-communicating hydrocephalus).
  • Multiple abnormalities such as brain tumours, congenital malformations and inflammatory lesions are associated with hydrocephalus.
  • In a patient with hydrocephalus, cerebrospinal fluid accumulation results in raised intracranial pressure which in turn results in enlarged ventricles and skull. Raised intracranial pressure is further associated with behavioural change, headache, papilloedema (oedema of the optic nerve) and herniation syndromes (subfalcine, uncal and cerebellar).
  • Enlargement of cranial sutures, progressive thinning of cerebral walls and lamination of cerebral cortex are all manifestations of hydrocephalus. Symptoms include significant deficits in motor skills (damage to pyramidal tracts) and cognitive functioning.
  • The extent of brain damage depends on the underlying factor and developmental stage in which damage occurs. Hydrocephalus can be treated by shunting the excess fluid from the lateral ventricles into the heart or peritoneal cavity.


Arachnoid cyst with hydrocephalus.jpg

Magnetic Resonance image showing arachnoid Cyst with Hydrocephalus [19]

Fetal Alcohol Syndrome

[20]

  • Severe alcohol consumption during pregnancy and especially at critical stages of development (i.e. just after neural tube closure) can result in fetal alcohol syndrome (FAS).
  • FAS is the most severe form of a spectrum of physical, cognitive and behavioural disabilities, collectively known as fetal alcohol spectrum disorders (FASD).
  • Mental retardation is the most serious abnormality associated with FAS. In addition, FAS is typically associated with central nervous system abnormalities, impaired sensation, impaired motor skills and lack of coordination.
  • Patients diagnosed with FAS have a small head size relative to height, and demonstrate minor abnormalities of the face, eye, heart, joints, and external genitalia. (image)
  • Ethanol in alcohol directly damages neurons by acting as an agonist for GABA receptors in the brain as well as interfering with many other receptors. Ethanol can also alter body’s metabolism by an indirect effect on neurons that modulate the secretion of hormones. In addition, it is postulated that malnutrition intensified by alcohol abuse is another cause of FAS since FAS is more common in individuals with low socioeconomic status.
  • Nutritional deficiency and alcohol abuse inhibit the metabolism of folate, choline and vitamin A which are necessary for neurodevelopment. Therefore supplementation of these three nutrients to mothers with Disorder Binge drinking or low socioeconomic status may reduce the severity of FAS.
  • Consequently, pregnant mothers need to be aware of the risk associated with consuming even small amounts of alcohol. FASD and FAS represent a serious problem for both the individuals and society but are easily preventable.

500px

Image showing Facial characteristics associated with fetal alcohol syndrome[21]

Neural Tube Defects

Defects which affect the either the brain or the spinal cord in which openings remain. Grastulation occurs in week 3 of embryonic development where specialized cells (dorsal side) structurally change shape leading to the formation of the neural tube. If the neural tube does not close or fuse together properly, then openings remain which lead to various neural tube defects such as Spina bifida cystica and Spina bifida occulta.

Anencephaly

  • A neural tube defect involving abnormal development of the brain and incomplete skull formation leading to high infant mortality rates with infants being stillborn or dying within a few hours after birth.
  • The failure of the neural tube to close around the 23rd and 26th day into embryonic development is characteristic of this condition. As a result, the forebrain is severely affected where the cerebrum does not grow and hence partial growth occurs only. The cerebrum has a key importance in maintaining thought, consciousness and coordination whilst having no intact cerebrum rules out the probability of the affected fetus gaining consciousness .
  • Increasing one's dietary intake of folic acid notably reduces the incidence of neural tube defects. Consuming 0.4mg of folic acid is sufficient to induce these results.
  • Since incomplete skull formation occurs, brain tissue becomes exposed due to the absence of bone covering and therefore leading to further complications.

Encephaloceles

  • Another neural tube defect in which a sac-like projections (including membrane covering) that occurs around the 3-4 week of embryonic development in which neural tube closure has not successfully occurred. The location of these protrusions varies but can be naso-frontal (nose and head), naso-ethmoidal (nose and ethmoid bone), naso-orbital (nose and eyes), meningocele (cerebrospinal fluid and membrane covering) and encephalomeningocele (meningocele with brain tissue as well).
  • These sac-like protrusions lead to a variety of abnormal effects which include cerebro-spinal fluid build-up in brain, microcephaly, hydrocephaly, mental retardation, developmental problems, uncoordinated muscle movement and seizures. Consumption of folic acid again has been shown to significantly reduce the occurrence of encephaloceles in infants.

Hydranencephaly

  • A very rare neural tube defect in which the cerebral hemispheres are destroyed (necrotic tissue) with the occupied space being replaced by cerebro-spinal fluid, cortex and white matter remnants within a membranous sac. Interestingly, this condition can also develop in the postnatal peroid due to viral infections or traumatic brain injury. The brain stem may remain intact and functioning in hydranencephalic infants.
  • Accompanied with this condition are many effects in which include seizures, hydrocephalus, increases in head circumference,impairment in vision/ body temperature regulation and cerebral palsy. Infants affected by hydranencephaly live typically short lives being no longer than 1 year of age. Lastly, there are no viable treatment options for this condition and only supportive care is available.

Iniencephaly

  • Another neural tube defect involving severe backward bending of the head (retroflexion) with subsequent spinal distortions as well. Affected infants have no neck and hence the scalp of the head is directly joined to the skin of the back (also skin of the face connected to skin of the chest). Other conditions that develop along with iniencephaly are cyclopia, cephalocele and anencephaly. The development of this condition is not solely due to one factor but from various causes (both genetic and environmental factors).
  • There are specific factors that have been shown to increase the occurrence of this condition. Malnutrition, reduced folic acid intake and elevated levels of homocysteine in blood are environmental factors that increase the risk of iniencephaly [22]. Intake of certain drugs such as anti-histamines and sulphonamide/tetracycline (antibiotics) have also increases this risk [23]. Furthermore obesity has been shown to have a significant effect on the incidence of iniencephaly with 1.7-3 fold increase [24].
  • In terms of treatment, folic acid supplementation as well as avoiding certain drugs such as those outlined above significantly reduces the occurrence of this condition.

Spina Bifida Cystica

  • A neural tube defect in which involves either the formation of a meningocele or myelomeningocele. Of the two, the meningocele, is the least debilitating in that a cyst-like structure forms when the neural tube does not close properly. The membrane (meninges) is pushed into openings of the vertebrae where spinal fluid builds up within the cyst. The myelomeningocele leads to severe problems as the portion of the nueral tube that is unfused allows the spinal cord to protrude through. As a result, neuronal tissue is highly exposed due to myeloschisis as well as infections and hence may lead to severe complications.

Spina Bifida Occulta

  • A neural tube defect that has minimal complications in comparison to other defects. Furthermore, this defect is hidden in that a tethered spinal cord may arise as well as a thicker filum terminale and diastematomyelia (spinal cord split into two). It is also important to note that no cysts form as opposed to the other more severe spina bifida defects.

References

  1. Report of the Workshop on Acute Perinatal Asphyxia in Term Infants, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Child Health and Human Development, NIH Publication No. 96-3823, March 1996.
  2. <pubmed>4203033</pubmed>
  3. <pubmed>7204662</pubmed>
  4. <pubmed>22272298</pubmed>
  5. <pubmed>17726524</pubmed>
  6. <pubmed>10532616</pubmed>
  7. <pubmed>19339620</pubmed>
  8. <pubmed>19339620</pubmed>
  9. <pubmed>11158907</pubmed>
  10. <pubmed>11158907</pubmed>
  11. <pubmed>20608424</pubmed>
  12. <Pubmed>17490748</pubmed>
  13. <pubmed> 21414909 </pubmed>
  14. <pubmed> 23307634 </pubmed>
  15. <pubmed> 23307635 </pubmed>
  16. <pubmed> 24812082 </pubmed>
  17. <pubmed> 23508710 </pubmed>
  18. <pubmed>3271622</pubmed>|[1]
  19. <pubmed>22069421</pubmed>
  20. <pubmed> 23809349 </pubmed>
  21. <pubmed> PMC3756137</pubmed>|[2]
  22. <pubmed> 22408660 </pubmed>
  23. <pubmed> 22439066 </pubmed>
  24. <pubmed> 18538144 </pubmed>