Lecture 1: Neuroembryology Neuroscience 1: Neuroembryology

Transcription

1 The nervous system starts to form at the 3 rd week of life from the ectoderm at the specialized part called the neuroectoderm/neurectoderm. The Notochord forms at the 3 rd week of life o It is the source of inducers The inducers seep into the overlying ectoderm and stimulate a cellular thickening and form the following structures in subsequent order: 1 Neural plate a Will indent to form #2 2 Neural groove a Will deepen to form #3 at the lateral margins 3 Neural fold a The edges of the neural fold will start to approximate each other and eventually fuse at the posterior midline, and then separate with the overlying ectoderm to form the #4: i However, before it separates from the overlying ectoderm, a portion of the neural folds will also separate from the surface ectoderm that will NOT move with the neural tube but rather position itself dorsolateral to the neural tube and this will be called the neural crest Neural crest gives rise to PNS 4 Neural Tube a Neural tube proceeds rostrally and caudally to form the anterior and posterior neuropores, respectively b Formation of the neural tube from neural plate gives rise to the brain and spinal cord up to lumbar levels c Layers of Neural Tube: i Ventricular Zone Progenitor cells of this layer gives rise to: o Neurons o Glial cells o Ependymal cells line ventricles ii Marginal Zone Contains processes of the cells located in the ventricular zone Does NOT contain nuclei by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 1 of 13

2 iii Intermediate Zone Formed in between the ventricular and marginal zones Nuclei from ventricular zone move into this layer with the processes extending to the marginal zone iv Mnemonic: Neural Tube Layers are VIM o The notochord defines the long axis of the developing embryo o The notochord determine the orientation of the vertebral column o The notochord also produces cell adhesion molecules (N-CAM or simply, CAM) so that cells in the overlying notochord will move as a single unit o In the adult, the notochord persists as the nucleus pulposus/pulpy nucleus located in the intervertebral disks between the vertebrae PRIMARY NEURULATION All the processes mentioned above: from neural plate to neural tube giving rise to the CNS (Brain+SC) is called primary neurulation Occurs at Day AOG Therefore, the neural tube is the primitive CNS o Rostral 2/3 gives rise to the brain o Caudal 1/3 gives rise to the SC (up to lumbar levels) o Caudal eminence gives rise to sacral and coccygeal segments Neural crest develops into the PNS o Derivatives: Schwann cells Cranial nerve ganglion Dorsal root ganglion Autonomic ganglion Chromaffin cells of Adrenal Medulla Pia and Arachnoid of meninges Melanocytes DISORDERS OF THE PRIMARY NEURULATION Dysraphic Effects congenital malformation associated with defective neurulation. Incidence of which can be reduced through supplementation of folic acid by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 2 of 13

3 A. Anterior Neuropore Anomalies 1. Anencephaly Literally means Without Brain Cause: failure of the anterior neuropore to close o Anterior neuropore closes at Day 24 o Anterior neuropore closes first before the posterior neuropore No neural tube in anterior aspect Brain is not formed, meninges are absent and skull, with abnormal fascies 100% mortality babies survive at most for 1 week No extraordinary measures given: Comfort, love, and prayers sorry baby love 2. Encephalocoele herniation of intracranial contents AKA Crania bifidum Types of encephalocoele (or encephalocele, whichever) o Meningocoele herniation of meninges o Meningoencephalocoele herniation of meninges + brain o Meningohydroencephalocoele herniation of meninges + brain + part of ventricular system 3. Arnold-Chiara Malformation The congenital herniation of the cerebellar vermis through the foramen magnum causing pressure on the medulla and cervical spinal cord B. Posterior Neuropore Anomalies Posterior neuropore anomalies are collectively known as myeloschisis 1. Spina Bifida failure of the vertebral arches to form completely and fuse to cover the spinal cord Types of Spina Bifida o Spina Bifida Occulta If there is skin covering the spinal cord Minimal defect o Spina Bifida Aperta If there is NO skin covering the spinal cord o Spina Bifida Cystica If there is a cystic mass accompanying the spina bifida 1 The cystic mass is protruding at the area of non-closure that can be a: a Meningocoele meninges + CSF b Meningomeylocoele meninges + CSF + spinal neural tissue (either Spinal Cord or part of the cauda equina) by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 3 of 13

4 i Meningomyelocoele causes loss of movement or sensation in areas below the lesion 2. Myelosrachischisis Open neural tube at the back High mortality Prognosis varies on the degree of defect There is functional impairment Preventive measures for all these dysraphic effects Supplementation of Folic acid daily (usually 400 micrograms) SECONDARY NEURULATION This is the formation of the sacral and coccygeal segments of the spinal cord that begins on Day 20 and ends on Day 42. Gives rise to sacral and coccygeal portions Appearance of caudal eminence caudal to the neural tube which enlarges and cavitates and this joins the neural tube to form a continuous neural canal o It is in the neck region where the neural fold starts to approximate each other and eventually form the neural tube during primary neurulation. It then proceeds rostrally and caudally along the length of the embryonic disc 1 There are rostral and caudal openings: a Rostral opening the Anterior Neuropore i Communicates the neural cavity with the amniotic cavity ii Closes first because the cervical region/neck is closer rostrally; Day 24 DISORDERS OF THE SECONDARY NEURULATION When the anterior neuroporecloses, it forms a membrane called lamina terminal b Caudal opening the Posterior Neuropore i Connects the caudal neural cavity with the caudal amniotic cavity ii Closes after the anterior neuropore at Day 26 Disorders of the secondary neurulation are termed to be as Myelodysplasias The site of myelodysplasia may be marked with: o Unusual pigmentation o Unusual hair growth by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 4 of 13

5 o Prominent dimpling of overlying skin Tethered Cord Syndrome Abnormality wherein the conus terminalis and filum terminale are abnormally fixed to the defective vertebral column thus affecting the exiting spinal nerves from the cord Loss of sensation in the lower extremities Urinary Bladder control problems The lower back is usually with: o Tufts of Hair o Violaceous in color o Prominent dimple It is more symptomatic than spina bifida BRAIN VESICLES Primary brain vesicles are formed during anterior neuropore closure (Day 24, 4 th week AOG). Prosencephalon forebrain Mesencephalon midbrain o Contains the mesencephalic flexure (cephalic flexure) that demarcates the midbrain from the forebrain Rhombencephalon hindbrain (cavity: 4 th ventricle) o Contains the cervical flexure a slight bend found at the rhombencephalon-spinal cord junction o Will form the: 1 Foramina of Magendie (Midline) 2 Foraminae of Luschka (Lateral) Both will be passageways of CSF 1 If the sylvian aqueduct is small, CSF will be shunted to these foraminae so quickly creating an obstructing hydrocephalus Mnemonic: Primary brain vesicles ay parang train because PMR (pnr train hahaha) by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 5 of 13

6 Secondary Brain Vesicles the 3 Primary Brain Vesicles (PBV) divide into 5 secondary brain vesicles (SBV) during 5 th week Figure 1. Primary Brain Vesicles becoming Secondary Brain Vesicles Note on development of Primary Brain Vesicles: Mesencephalon does NOT divide further it is retained o Therefore, the a distinction should be when referring to the mesencephalon specify with either Primary/Secondary Brain Vesicle Prosencephalization o Process wherein the prosencephalon is divided into the Diencephalon and Telencephalon via the Telencephalic Flexure o Diencephalon the Thalamic family (cavity: 3 rd ventricle) Adult Derivatives: 1 Thalamus, Epithalamus, Hypothalamus, Subthalamus 2 Pineal gland 3 Retina 4 Optic Nerve 5 Mamillary bodies o Telencephalon expands to form the following structure and therefore becomes the largest part of the brain (cavity: 2 lateral ventricles): Adult Derivatives: 1 Cerebral hemispheres including cortex and medullary centers a Lobes (Occipital, frontal, etc) b Gyri c Sulci 2 Olfactory system 3 Hippocampus 4 Corpus striatum 5 Lamina Terminalis by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 6 of 13

7 6 Basal Ganglia The telencephalic vesicles become the primordia of the cerebral hemispheres. And the adult derivative: Cerebral Cortex o Failures of Prosencephalization failure of the prosencephalon to undergo cleavage: Alobar prosencephaly no discernable lobes develop 1 You cannot demarcate where is the temporal lobe from the occipital from the etc etc Semilobar holoprosencephaly there is some degree of separation; occipital areas are usually prominent Fates of other secondary brain vesicles: o Mesencephalon midbrain (cavity: sylvian aqueduct) o Metencephalon: Pons Cerebellum o Myelencephalon medulla oblongata Choroid Plexus blood vessel inside the ventricle, responsible for the production of CSF(?) During the development of the ventricles, the blood vessel that is outside will dig inside bringing with it meningeal layers (PAD) o This is why meningioma can originate inside the ventricles There are certain infections acquired by the pregnant mother that can cause congenital nervous system (especially neural tube defects) defects to the baby : TORCH o Toxoplasma o Others (Syphilis by Treponema pallidum) o Rubella virus o Cytomegalovirus o Herpes simplex virus DEVELOPMENT OF THE SPINAL CORD The spinal cord is formed from the caudal portion of the neural tube Neural canal becomes the central canal of SC Transverse Differentiation of Primitive Neural Tube Neural tube initially exists as a single layer of pseudostratified columnar epithelium with intense proliferative activity Again, three layers: VIM Ventricular Zone (Ependymal Zone) Inner Layer o Cellular layer Marginal Zone Outer Layer by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 7 of 13

8 o Acellular layer, ONLY process Intermediate Zone (Mantle Zone) Middle layer o Cellular layer The Intermediate Zone AKA Mantle Layer Grows asymmetrically Contains the Sulcus Limitans o A demarcation separating the proliferating cells from: Dorsal Half Ventral Half o Dorsal to the sulcus limitans are structures that will comprise the alar plate Alar plate is the posterior portion of the ventricular zone 1 AP will give rise to the Dorsal Root Ganglion (DRG) a DRG is sensory in function b DRG receives processes from the pseudounipolar neurons forming the dorsal root of the spinal nerve o Ventral to the sulcus limitans are structures that will comprise the basal plate Basal plate is the anterior portion of the ventricular zone 1 BP gives rise to the anterior horn a Anterior horn is motor in function b Anterior/ventral gray horn sends axons to form the ventral root of the spinal cord to supply a specific myotome level o How about the marginal zone? Will become the white matter of the SC The Spinal Cord Each cord segment will be supplying a specific area of the skin called a dermatome As the anterior/ventral gray horn is developing, it will form the anterior root of the spinal nerves which would supply a specific group of muscles called myotome of that specific cord segment o As the cord is developing, the spine is also developing However, at 2 nd trimester and at birth, the SC is shorter than the vertebra indicating faster growth rate of the bony vertebra 1 There is a discrepancy in length of the cord and the length of the vertebra, so much so that the cord is almost at the level of L2 only a Therefore, the first sacral nerve will have to travel a longer way to reach S1 At birth, the SC is at L1 In the adult, the SC is between L1-L2 by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 8 of 13

9 Nerve Termination This phenomenon is biochemically dictated. o Structures derived from the neural crest contain in their surface integrins which recognize specific molecule in the connective tissue at a specific dermatome level, which in turn contains fibronectin/laminin containing a specific amino acid sequence. This mechanism enables the integrins to know where to terminate DEVELOPMENT OF THE BRAINSTEM Consists of the myelencephalon, pons, and mesencephalon o Myelencephalon gives rise to medulla oblongata Has a portion which is similar to the spinal cord and a portion where the neural cavity opens to become the 4 th ventricle 1 Spinal-cord like medulla all structures dorsal to the sulcus limitans such as the sulcus gracilis and nucleus cuneatus are alar plate-derived and have sensory function a The gracilis is for conscious proprioception on the legs b The cuneatus would be conscious prioprioception of UE and the trunk Upper 1/3 of Medulla the cavity there opens to form the 4 th ventricle 1 Because of the opening of the cavity to become the ventricle, the alar plate becomes rotated dorsolaterally and becomes lateral to sulcus limitans 2 As for the basal plate, it will now become medial to the sulcus limitans Lower 2/3 of Medulla alar is now posterior/dorsal while basal ventral/anterior Cranial Nerves of Medulla 1 CN 7,9, 10 forms the nucleus solitarius for taste 2 Descending nucleus of CN 5 for facial sensation 3 CN 9-12 can be found in the Myelencephalon DEVELOPMENT OF THE CEREBELLUM Arises from the rostral portion of the rhombic lip (alar structure that forms part of the wall of 4 th ventricle) o Rhombic lip is: Proliferative; as it starts to row further, it would meet with the rhombic lip of the other side and cover the posterior surface of the 4 th ventricle to give rise to the cerebellum Caudal part gives rise to the inferior olivary, cochlear, and pontine nuclei by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 9 of 13

10 Has Inner white matter, outer gray matter Cells from the intermediate zone would migrate using the radial glial cells as scaffold to hold on to while they migrate external to the marginal zone to form the external granular layer o From this layer, the following will be formed: Granule cells Stellate cells Basket cells From the original intermediate zone, the cells would also migrate but they migrate outward and would give rise to the deep cerebellar nuclei and purkinje cells The posterolateral fissure develops first before the primary fissure o Posterolateral fissure divides the cerebellum into the: Flocculonodular lobe Corpus cerebelli o Primary fissure divides the corpus cerebelli into: Anterior lobe Posterior lobe DEVELOPMENT OF THE THALAMIC FAMILY (DIENCEPHALON) The mature diencephalon cannot be seen externally because it is covered by the cerebral cortex. Thus, one would have to will have to dissect the brain sagitally or coronally The diencephalon is largely derived from the alar plate The diencephalon gives rise to: o Epithalamus o Hypothalamus o Thalamus Development occurs in an outside-first sequence (Lateral nuclei develop first, medial ones last) 1 First neurons to undergo final cell division migrate to the outermost portion of the thalamus a Generated first are the lateral nuclei: i Geniculate nuclei ii Lateral nuclei iii Ventral nuclei b Generated last are the medial nuclei: i Dorsomedial nucleus 2 Radial glia serves as a guide for migration by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 10 of 13

11 DEVELOPMENT OF THE CEREBRAL CORTEX (TELENCEPHALON) Development pattern is inside-out The outer gray has 6 layers Formation of the cortical plate at interface of marginal-intermediate zones o Marginal zone gives rise to layer 1 of cerebral cortex o Cortical plate gives rise to layers 2-6 of cerebral cortex Formation of the subplate a narrow region internal to the cortical plate o Subplate and intermediate zone gives rise to subcortical white matter 1 st trimester hallmark of a normal brain to have gyri+sulci/fissures o Due to the limited space in the skull, when brain tissue encounters resistance it would fold forming gyri and sulci o More neurons buried inside the sulci and fissure o 1 st trimester fissures: Interhemispheric fissures Sylvian fissure Central sulcus o 8 th month fissures: Secondary sulcus o 3 rd trimester fissures: Tertiary/all sulci are formed Cerebral cortex is the higher centers for critical thinking, imagination, analysis, etc Abnormalities: o Lissencephaly failure of gyri to form creating a smooth surfaced cortex o Pachygyria unusually large gyri o Microgyria unusually small gyri o Scizencephaly abnormal patterns of sulcal and gyral development with unilateral or bilateral clefts in cerebral hemisphere VENTRICULAR SYSTEM Normally, should be patented so that the CSF can circulate Any abnormality in the ventricular system is called hydrocephalus o Treated by shunting the flow of the CSF Otherwise, the trapped CSF will cause pressure in the developing neurons and they atrophy o Obstructive Non-communicating Hydrocephalus When there is atresia of the cerebral aqueduct, the CSF canot circulate, there will be dilation proximal to the obstruction 1 Due to: Congenital aqueductal stenosis o Non-obstructive Communicating Hydrocephalus No obstruction but there is abnormality in the transfer of the CSF from the subarachnoid to the venous system by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 11 of 13

12 PARAMETERS IN BRAIN ORGANIZATION Density or Number of Neurons o Neurons terminally differentiated and thus, they will not undergo mitosis 6 months AOG: 1 There is overproduction of neurons. After which, there will be selective apoptosis of neurons that are not good/useful Pattern of Axon and Dendrite Branching o Age 2-3 y/o complete neurons with dendritic and axonal branching Pattern of Synaptic Contacts o Occurs throughout life o Neurons are always open to new learning synaptic contacts can be fashioned/remodeled Lumosity o Factors affecting synaptic stabilization Critical period refers to time period when these types of plastic changes occur varies from region to region 1 Ex: Baby with congenital cataract or severe myopia of left ey a As the baby grows, the impulses from the right eye would have to establish synaptic stabilization in the visual centers in the cortex b But since the left eye is severely myopic, whatever stimulation it receives is not enough to send synaptic contact to the cerebral cortex c If this is not treated early, the entire visual cortex will be taken over by the good eye so much that if later, corrective lenses are given, they re going to be useless since the visual cortex has been taken over by the synaptic contacts made by through the right eye Synaptic Development Parallels cellular proliferation and migration Maximal period is during six months after birth o Vulnerable to: Perinatal hypoxia Malnutrition Environmental toxins Myelination Peak: From six months after birth to first year of life Continues into adulthood Motor and sensory tracts mature early Affected by: o Leukodystrophy o Phenylketonuria o Malnutrition by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 12 of 13

13 o Impaired Lipid Metabolism Plasticity Alteration in selective neuronal death, axonal simplification and retention of transient axonal branches and synapses that would otherwise be lost Therefore, the developing bran is not as vulnerable to injury as the mature brain o Critical period: The period of time during which plastic changes can occur. If the critical period is over, then changes become permanent References -end- 1. Lecture notes by RAsturiano (A-2019) from the lecturer 2. Transcription notes by Carmella Agcaoili (A-2019) 3. Super subsec notes 2015 Downloadable for free at: For any corrections you may find, content or otherwise, me at: ram.ustmedicine@gmail.com -THANKS- By RAsturiano #TheElusiveDoktora by RAsturiano UST-FMS A-2019: #TheElusiveDoktora Page 13 of 13