Neuroscience LC2: Neuroglial Cells and Glial Cells in Pathology (2028)

ll COURSE OUTLINE II. CLASSIFICATION OF NEUROGLIAL CELLS I. Main Cells of the Nervous System A. Nerve Cells...

ll COURSE OUTLINE II. CLASSIFICATION OF NEUROGLIAL CELLS I. Main Cells of the Nervous System A. Nerve Cells A.IN THE CNS B. Neuroglial Cells Astrocytes II. Classification of Neuroglial Cells ○ Protoplasmic A. In the CNS ○ Fibrous B. In the PNS Oligodendrocytes III. Gliogenesis ○ Perineural satellite cell IV. Neuroglial Cells in the CNS ○ Interfascicular cell A. Astrocytes Ependymal cells B. Oligodendrocytes ○ Ependymocytes C. Ependymal Cells ○ Tanycytes D. Microglial Cells ○ Choroidal epithelial cells V. Neuroglial Cells in the PNS Microglial cells A. Schwann Cells B. Satellite Cells B. IN THE PNS VI. Blood Brain Barrier Schwann cells VII. Differences of CNS and PNS Myelin ○ In peripheral nerve VIII. Glial Cells in Pathology Satellite cells IX. Wallerian Degeneration ○ In ganglia/ganglion X. Demyelination III. GLIOGENESIS The generation of glial cells from progenitor I. MAIN CELLS OF cells that generate neural cells (neuroepithelial THE NERVOUS SYSTEM stem cells) Occur during development of the central A. NERVE CELL nervous system when neural progenitor cells switch to generating glial cells following the NEURONS generation of neurons (neurogenesis.) ○ Structural and functional unit of the Microglial cells are derived from nervous system. HEMATOPOIETIC STEM CELL/analog of the ○ Specialized to: macrophages in the blood. Conduct electric signal/impulses Aside from Microglia, ALL glial cells (like through its membrane neurons) are derived from the Communicate via chemical synapses NEUROECTODERM. with other neurons. Ionic/electrical transmission happens only in the membranes of the neurons in order for that action potential to affect the release of neurotransmitters in the axonal end tip. B. NEUROGLIAL CELLS Glial ○ Metabolic and mechanical support for neurons ○ 10:1 more abundant than neurons ○ Undergo mitosis replace damaged glial cells Figure 1. Gliogenesis With centrioles Incapable of action potential generation thus IV. NEUROGLIAL CELLS IN THE CNS incapable of synapse communication Glial cells DO NOT carry nerve impulses (action potential), but without them, the neurons would not work properly Figure 2. Neuroglial Cells in the CNS and the PNS BATCH 2028 1F 1  NEUROSCIENCE LC 2 Neurotransmitter Decreased neurotransmitter A. ASTROCYTES uptake and recycling uptake and/or recycling From the Greek word Astron, meaning a “star” Synapse formation, Decreased synapse Most abundant, largest, versatile, highly branched maturation and formation and altered glial cells function neuronal activity ○ 30-50% of brain volume Regulation of blood Increased immune cell ○ Clings to neurons and cover capillaries and glymphatic flow infiltration and blood-brain PLASMACYTOMA (most common maintenance and/or repair tumor that comes from astrocytes) Post-mitotic Proliferate and form scars Summary of Functions: or borders ○ Support and braces neurons Interaction and Corral peripheral immune ○ Anchor neurons to their nutrient supplies coordination with cells and/or amplify (Capillaries) immune cells inflammatory responses ○ Guide migration of young neurons during Stable and rhythmic Irregular calcium transients, development calcium transients decreased gap junction ○ Control the chemical/ionic environment coupling ○ Responsible for scar formation ○ (“Gliosis” after trauma/stroke) ○ Energy metabolism ○ Forms the blood brain barrier Controls the level of neurotransmitters around your synapses to the synaptic resolution of your neurons ✓ Maintain blood-brain barrier ✓ Regulate ion, and provide metabolic support ASTROCYTOSIS / GLIOSIS ○ astrocytes proliferation Figure 3. Histology of Astrocytes Figure 4. Morphological and functional associations of Astrocytes Postsynaptic neuron NORMAL ASTROGLIAL FUNCTIONS: ○ releases neurotransmitter via receptors - ○ astrocytes regulate the synaptic connection Developmental There is no synaptic impulse when there is no ○ Migrational and axon guidance of neuron synaptic capability to communicate with the Homeostasis neuron. ○ Neuronal microenvironment / Ionic and ➔During disease, these glial cells will perform metabolic neurotransmitter uptake different functions: Blood Brain Barrier With the supporting neuron, glial cells are ○ Induction and Maintenance responsible for reconnecting neurons by finding Trophic other neurons in order to form a synapse again. ○ Support of Neurons (Providing Growth They are also attached to blood vessels which Factor) transfer the nutrients towards the neurons. Synaptogenesis: They also form the blood brain barrier covering ○ Synaptic Modelling/ Control or Aid in the blood vessels. Synapse formation They form a regulating function in the synapses ○ Synaptic neuron regulates the by providing a bridge between neurons and neurotransmitter. blood vessels. ASTROCYTES have virtual contact with every other cells in the brain (with both neurons and glial cell) TABLE 1. FUNCTIONS OF PHYSIOLOGICAL AND REACTIVE ASTROCYTES PHYSIOLOGICAL REACTIVE ASTROCYTE ASTROCYTE FUNCTIONS FUNCTIONS Neuron trophic support No or decreased trophic support or active Figure 5. Astrocytes in Electron Microscope neurotoxicity BATCH 2028 1F 2 NEUROSCIENCE LC 2 TYPES OF ASTROCYTES: Protoplasmic - found in Grey Matter a. Structure: Small cell bodies, short thick processes, many branches, few cytoplasmic filaments, perivascular feet b. Functions: store glycogen, have a phagocytic function, take place of dead neurons, conduit for metabolites/ raw materials, produces trophic substance Fibrous Astrocyte - found in White Matter a. Structure: Small cell bodies, long slender Figure 8. Muller Cell processes, cytoplasmic filaments, perivascular feet b. Functions: provide supporting framework, are electrical insulators, limit the spread of neurotransmitters, take up of K ions (a) Figure 6. Types of Astrocytes SPECIALIZED ASTROCYTES Bergmann’s glial cell ○ in support of Purkinje cell of cerebellum PURKINJE CELLS - largest neurons in the body (located in the cerebellum) Functional unit of cerebellum For balance and coordination Muller Cell ○ homeostatic and metabolic support of retinal cells part of the retina Pituicyte ○ modified glial cell in Pituitary gland supports the neurons in the Pituitary Glands Figure 9a & 9b. Pituicyte Figure 7. Bergmann’s Glial cell BATCH 2028 1F 3  NEUROSCIENCE LC 2 PARTS OF ASTROCYTES Target of autoimmune attacks in (Multiple sclerosis - demyelinating disease) Cell body Myelin Specific Oligodendrocyte Protein (MOSP) ○ shaped nucleus, scarce pale Cytoplasm - Tumor marker Processes Exclusively expressed in CNS Myelin express GFAP (Glial fibroacidic Analog of the Schwann cell (PNS) in the Central protein) Nervous System. Key intermediate filament (IF) III protein Responsible for forming myelin sheaths in the responsible for the cytoskeleton CNS axons structure of glial cells and for ○ Around the brain and spinal cord axons. maintaining their mechanical strength, ○ Myelin is an electrical insulator which speeds as well as supporting neighboring up conduction. neurons and the blood brain barrier (BBB) OLIGODENDROCYTES UNDER THE - Astrocyte specific marker MICROSCOPE Their processes are functionally coupled at gap junctions. Looks like a bicycle wheel. The main body of the cell is in the center with lots of 'spokes' that have Perivascular feet (foot processes/ vascular end short lengths of myelin at the ends. feet) Oligodendrocytes can have up to 60 of these ○ Surrounds blood vessels (BBB) or attach to spokes. axon (Synapse) Figure 12. Oligodendrocytes Figure 10. Perivascular feet MYELINATION Pedicles wraps capillaries and binds to the pia mater to form Myelination begins during fetal development and ○ Pia Mater - meninges proceeds most rapidly in infancy. Completed in A vascular membrane covered by adulthood. flattened mesothelial cells. ○ Glial Limitans ○ Forms the BBB (Blood - Brain Barrier) ○ Prevent toxins/ certain drugs from entering the brain ○ A filter or gatekeeper amoxicillin (cannot enter the blood-brain barrier) Figure 13. Myelination Baby neuron - mature, very few or still not myelinated. Teenage Neuron - myelination progress Adult Neuron - perfect myelination of axon. Capable of faster production, more stable conduction creates more stable connections with other neurons. Figure 11. The Blood - Brain Barrier MYELIN PRODUCTION Oligodendrocytes develop from an Oligodendrocyte progenitor cell (OPC) by B. OLIGODENDROCYTES extending its processes and ultimately forming "Few branch Glia" sheet-like myelin protein containing protrusions. ○ oligo = Few A single cell wraps around multiple axons thru its ○ Dendrocytes = branches processes. Discovered by Del Rio Ortega in 1921 using Up to 60 axons can be wrapped by a single metallic impregnation techniques. cell. BATCH 2028 1F 4  NEUROSCIENCE LC 2 Cuboidal to columnar ciliated epithelial cells. Lines the ventricles of the brain and central canal of the spinal cord. Forms the Choroid plexus in the lateral ventricles. Main production of Cerebrospinal fluid (SF) Facilitates distribution of CSF. EPENDYMAL CELL TYPES Figure 14. Myelin production 1. Ventricular Epithelial Cells In the presence of axon oligodendrocyte Lining ventricular surface (Line the ventricles progenitor cells extend their processes, and upon of the brain and the central canal of the spinal contact formation with axons initiate a wrapping cord and are in contact with the cerebrospinal process, which will subsequently form the fluid) compact myelin sheath. Cilia and microvilli on luminal surface Cuboidal to low columnar ciliated epithelial OLIGODENDROCYTES IN SUMMARY cells 2. Tanycyte Produce myelin in the CNS Nutrient-sensing cells that line the 3rd ventricle A single Cell wrap several axons ( up to 60 over-lying the median eminence of axons) hypothalamus. Also forms the nodes of Ranvier which are more Glucosensitive and are able to respond to widely spaced in CNS compared to PNS. transmitters associated with arousal and the drive to feed. They are thought to transport chemical substances from the CSF to the hypophyseal portal system. 3. Choroid plexus epithelial cells (Choroidal epithelial cells) Ion transporting cell, with numerous mitochondria. Responsible for cerebrospinal fluid production and secretion. The presence of tight junctions prevents the leakage of CSF into the underlying tissues Figure 15. Oligodendrocyte making myelin C. EPENDYMAL CELLS Figure 18. Ventricular lining Figure 16. Ependymal cells lining the CSF Figure 17. Ependymal cells lining the central canal Figure 19. Central canal of spinal cord BATCH 2028 1F 5  NEUROSCIENCE LC 2 are normally not phagocytic in this state. Figure 20. Choroid plexus Figure 22. Inactive microglial cells II. Under some pathological conditions, like bacterial D. MICROGLIAL CELLS infection, traumatic brain injury, stroke or Alzheimer’s; neurodegeneration occurs. Figure 21. Microglial cells found in the CNS Figure 23. Microglial under pathological condition Immune effector cells “Policemen” of the CNS III. Release of Inflammatory substances, activating Smallest and rarest glial cell (on the microglial cells thus becoming amoeboid in standby/Resting/Inactive in health, active during shape that will kill and engulf/eat the apoptotic disease), ovoid, with spines (dead) cells or pathogens. The only neuroglial cells that does not come from neuroepithelial cells, because they are derived from the hematopoietic stem cells (Mesenchymal) Macrophage (Mononuclear Phagocytic) System Origin:Blood Monocyte They increase in inflammation Parts of a Microglial cell: Figure 24. Active microglial (amoeboid in shape) ○ Cell body: - Slender, indented, heterochromatic (a) nucleus, dark cytoplasm - Prominent secondary lysosomes ○ Processes: - Short, highly branched Functions: ○ Phagocytize neuronal debris, microorganisms and acts as a protection for viruses and microorganisms ○ Part of the inflammatory response ○ Scattered throughout CNS clearing any debris ○ Responsible for the elimination of microbes, (b) dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS ○ Includes signaling cascades involving cytokines and chemokines ○ Responsible for Neurodegeneration (they are the ones who eat dead neurons) ○ Significant role in neurodegenerative diseases (eg. Alzheimer's, Parkinsons) ○ In pathological states release proinflammatory mediators like cytokines, interleukins, TNF-alpha etc., which are only released Figure 25 a&b. Microglial’s Immune response process during an inflammation, tumor, edema, etc. Identifying Microglial Cells ACTIVATION OF MICROGLIAL CELL ○ In the normal human brain, microglial cells express and can be demonstrated by using I. Inactive microglial cells in normal state are called Lectin RCA-1 (Ricinus communis Ramified or Resting microglial cells, and they agglutini-1) using avidin-biotin peroxidase BATCH 2028 1F 6  NEUROSCIENCE LC 2 method. Protection of the axon ○ Immunotherapy Electrically insulating fibers from one Injecting pathogen inside the cancer cell another so that the body will now identify the Increasing the speed of nerve impulse cancer cell as a pathogen, Because transmission cancer cell will trick the immune system to In the PNS, the myelin sheath is formed by the identify itself as a normal cell, and with Schwann cells immunotherapy the cancer cell will now be Schwann cell: identified as a pathogenic cell by the ○ Envelopes an axon in a trough immune system thus eliciting phagocytosis ○ Encloses the axon with its plasma membrane to the cancer-now pathogenic cell. ○ Concentric layers of membrane make up the V. NEUROGLIAL CELLS IN THE PNS Myelin sheath Neurilemma A. SCHWANN CELLS ○ Remaining nucleus cytoplasm of Schwann cell. ○ ✓ Speed of conduction is faster in the PNS as Also known as Lemmocytes compared to CNS Schwann cells are the analogue of Basal Lamina/Neurilemma oligodendrocytes in the PNS. ○ Remnants of the nucleus/cytoplasm of Schwann ✓ found only in the PNS cells Wraps around individual segment of a single axon Allows axonal repair in the PNS ( Axon Segment ) A single schwann cell will wrap (Peripheral Nerves and Cranial Nerves can around a single segment of the axon be reattached ✓due to the presence of ○ They wrap individually around the shaft of endoneurium) peripheral axons, forming a layer or myelin Absent in the CNS (White matter fiber tra sheath along segments of the axon. (more cts)Oligodendrocyte lack the compact) neurilemma/basal lamina of a schwann cell ○ Saltatory conduction via Nodes of Ranvier Repair not possible The Schwann cell membrane, which forms the Cannot reattach tracts in the brain and myelin sheath, is composed primarily of lipids spinal cord (called neurilemma / basal lamina – will wrap around the axon concentrically; enveloping a single schwann cell – 1 segment : 1 axon); the lipid serves as an insulator thereby speeding the transmission rate of action potentials along the axon. Figure 28. The basal lamina or neurilemma Both motor fiber and sensory fiber is wrapped by schwann cell, both have saltatory conduction Sensory conduction – Towards the CNS; towards the dorsal root ganglia Motor conduction – Away from the CNS; towards the neuromuscular junction Figure 26. Structure of Schwann Cells Schwann cell found beneath the endoneurium, wrapping the segment of the axon. The fascicle is MYELIN SHEATH AND NEURILEMMA wrapped by perineurium. ✓ The whole nerve is wrapped by epineurium. Figure 27. The myelin sheath and the neurilemma formation in the PNS Myelin Sheath and Neurilemma: Formation (PNS) Figure 29. A cut section of a nerve. The endoneurium, ○ Whitish, fatty (Protein-lipoid), segmented sheath perineurium, and epineurium around most long axons ○ It functions in: Peripheral nerves is a collective term for the BATCH 2028 1F 7  NEUROSCIENCE LC 2 cranial and spinal nerves. Each peripheral nerve A. SATELLITE CELLS consists of parallel bundles of nerve fibers, which may be efferent or afferent axons, may be Analog of astrocytes in the PNS myelinated or unmyelinated, and are surrounded Wraps around nerve cell bodies in the: by connective tissue sheaths. ○ Sensory Ganglias (dorsal root ganglia) The nerve trunk is surrounded by a dense cell bodies: pseudounipolar neurons connective tissue sheath called the epineurium. ○ Autonomic Ganglias (sympathetic and Within the sheath are bundles of nerve fibers. parasympathetic) Each of which is surrounded by a connective cell bodies: pseudounipolar neurons but tissue sheath called the perineurium. Between motor neurons the individual nerve fibers is a loose, delicate Regulates the microenvironment in these connective tissue referred to as the ganglias endoneurium. The connective tissue sheaths Nutrient supply / structural function serve to support the nerve fibers and their associated blood vessels and lymph vessels. (Snell’s Clinical Neuroanatomy. 8th edition) SCHWANN CELL HISTOLOGY Figure 32. Satellite cell on the Dorsal Root Ganglion Figure 30. The individual nerve fibers wrapped individually in a segment Figure 33. The Satellite cells and the cell bodies of sensory neurons VI. BLOOD BRAIN BARRIER FORMED BY: ○ Endothelial cells of the capillary wall ○ Astrocytic endfeet (foot processes) ensheathing the capillary ○ Pericytes embedded in the capillary Oligodendrocytes – single cell wraps multiple basement membrane axons and multiple segments (around 60). FUNCTIONS: Widely spaced. ○ Highly selective semipermeable border that separates the circulating blood from the brain and extracellular fluid in the CNS ○ Allows selective passage by passive diffusion: nutrients, glucose, H2O, amino acids, HYDROPHOBIC MOLECULES like O2,CO2 and HORMONES- all crucial to Neural function Figure 30. Multiple axons wrapped by oligodendrocytes ○ Allows uncharged and lipid soluble molecules; allows alcohol, nicotine, and some drugs including anesthetics ○ Prevents entry of large hydrophilic neurotoxins and pathogens like bacteria NO BBB: ○ Circumventricular organs (CVO): Participating in sensory, neuroendocrine and secretory integration within neural circuits) ○ Choroid plexus - Produces Cerebrospinal fluid (CSF) Figure 31. Schwann cells around an axon - Allows passage of blood Schwann Cells – wraps around individual Circumventricular Organs (CVO) segments of a single axon (Axon segment). ○ Devoid of BBB Several Schwann cells wrap around a single ○ Permeable CVOs devoid of BBB enabling axon. rapid neurohumoral exchange include the: Subfornical organ Area postrema BATCH 2028 1F 8  NEUROSCIENCE LC 2 - Vomiting center TABLE 2. NEUROGLIAL CELLS IN CNS AND PNS - Located near the 4th ventricle Vascular organ of lamina terminalis CNS PNS FUNCTION Median eminence Astrocyte Satellite Cell Supportive Pituitary neural lobe (posterior pituitary) Pineal gland (subthalamus) Oligodendrocyte Schwann Cell Insulation, Parts of the Diencephalon Myelination ○ Thalamus Microglia Immune, ○ Hypothalamus phagocytosis ○ Pineal gland 5 Basic parts of the CNS Ependymal cell CSF production ○ Brain ○ Diencephalon ○ Brain stem ○ Spinal cord ○ Cerebellum VII. DIFFERENCES OF CNS MYELIN AND PNS MYELIN CNS MYELIN PNS MYELIN More Glycolipids Less Glycolipids Less Phospholipids More Phospholipids Lack basal laminae and With basal Laminae and Neurilemma of the Neurilemma Figure 35. Summary of the neuroglial cells in the CNS and PNS schwann cells VIII. GLIAL CELLS IN PATHOLOGY CNS fibers Lacks With endoneurium endoneurium covering GLIAL CELLS Glial cells are capable of reproduction/mitosis. Tracts have no layers of Have layers of They are actively dividing. connective tissue connective tissue When control over this capacity is lost (either covering (The reason covering (Epineurium genetically or an insult), primary brain tumors why you do not repair a /Perineurium) result. tract, why you do not GLIOBLASTOMAS/GLIOMAS repair an axon that is Glioblastoma is a malignant form that is already myelinated by Grade 4. oligodendrocyte) Astrocytoma – most common Widely spaced nodes of Closely spaced nodes of Oligodendroglioma Ranvier (The saltatory Ranvier Ependymoma/ Ganglioglioma conduction is more ➔ Grade 1 (best prognosis) - 4 (worst prognosis) distant to one another ➔ Are amongst the most deadly or malignant forms because they have of PRIMARY BRAIN CANCER more widely space ➔ Still, the most common brain cancer is axonal segment) metastatic. ➔ The cancer that has the highest propensity to Impulses are Impulses are (metastasize) go to your brain is melanoma (mole). conducted via saltatory conducted via saltatory conduction conduction IN THE PNS MYELIN One axon is myelinated by several Schwann cells in segments ○ A single axon wraps a single segment Figure 36. WHO glial tumor classification Figure 34. The myelinated axons, myelin sheath, Schwann cells, and the closely spaced nodes of Ranvier BATCH 2028 1F 9 NEUROSCIENCE LC 2 Figure 37. WHO Classification of Tumors of the CNS, fifth edition Figure 40. Post-op MRI: Complete Excision Now the brain looks normal - one month after operation. Pathologic insults to the brain: trauma, stroke, diseases, MS, encephalitis, etc) What is common among these diseases? There will be an inflammatory response. A hallmark of these inflammatories is the release of your GFAP. ○ Glial fibrillary acidic protein (GFAP) is the hallmark intermediate filament (IF; also known as nanofilament) protein in astrocytes, a main type of glial cells in the central nervous system (CNS). Figure 41. Pathophysiology of an insult to the NS: Hallmark increase in GFAP Figure 38. Tumor with micrometastasis This tumor in the frontal lobe is about 6 cm in diameter. Figure 42. More reactive astrocytes (gliosis) Astrocytes in reactive gliosis after insult (Diseases, trauma, stroke, etc) Prominent expression of intermediate filaments "glial filaments" Others: Vimentin, Synemin, and Nestin Astrocytes promote rewiring: axosomatic or dendrodendritic. Astrocytes have a range of control and Figure 39. Pre-op MRI of a 20-year-old Female homeostatic functions in health and disease. Astrocytes assume a reactive phenotype in acute CNS trauma, ischemia (stroke), and in neurodegenerative diseases. This coincides with an upregulation and rearrangement of the IFs, which form a highly complex system composed of GFAP (10 isoforms), vimentin, synemin, and nestin. We BATCH 2028 1F 10 NEUROSCIENCE LC 2 begin to unravel the function of the IF system of astrocytes IX. WALLERIAN DEGENERATION Acts as the crisis-command center - coordinating Degeneration of axons separated from their cell cell responses in situations connected to cellular body following nerve injury (Waller, 1850) stress, which is a central component of many neurological diseases. IN THE CENTRAL NERVOUS SYSTEM Table 3. Wallerian in CNS. Normal myelinated axon Distal to transected axon Axon degenerates Myelin disintegrates Myelin fragmentation Microglia activated Macrophages enter and remove debris Astrocytes and NG2- glia are activated Abortive regrowth Growth of the distal stumps of the transected Figure 43. Microglial Cells axons is inhibited Microglial cells - change in morphology in the Myelin debris is not presence of a pathogen or insult to the brain. removed Oligodendrocytes survive Damaged neurons are eaten by microglial cells Astrocytes and NG2-glia like pacman “paglilinis” form a glial scar Regeneration fails A consolidated glial scar (gliosis) forms and blocks regeneration Astrocytes form a glial scar to prevent regeneration of severed axons. When an axon is cut, they lose the neurilema basal In abortive regrowth, transcended axons will not grow because they lack neurilemma. Figure 44. Microglial cells change in morphology when activated. Microglial cells are resting “ramified” which normally should not be seen in the brain. When active - becomes phagocytic - amoeboid in shape. Figure 46. The ascending and descending tracts Sensory tract: Ascending - carry sensory information from the body, like pain, for example, up the spinal cord to the brain. Figure 45. Microglial cells become an amoeboid (phagocytic) in shape when activated. BATCH 2028 1F 11 NEUROSCIENCE LC 2 Figure 47. Spinal cord cross section Figure 49. Nerve impulse pathway IN THE PERIPHERAL NERVOUS SYSTEM TABLE 5. EVENTS THAT OCCUR DURING WALLERIAN DEGENERATION IN THE PNS Normal myelinated Motor Axon Distal to Transected Axon degenerates Myelinating Schwann Figure 48. Parts of the ascending and descending tracts cells 'dedifferentiate Myelin fragmentation Motor tract Descending - carry motor information Macrophages enter and like instructions to move the arm from the brain remove debris down the spinal cord to the body. Central Schwann cell basal canals- the H part - inner Gray matter- you can lamina find cell bodies here (e.g dendrites) tube remains intact ○ White matter- composed of axons (tract) Regeneration TABLE 4. THE SPECIFIC ASCENDING AND Proximal axons sprout DESCENDING OF THE BODY and grow into basal lamina Ascending tracts Descending tracts tube Schwann cells line up (Band of Bungner) and Lateral Spinothalamic Corticospinal produce growth factors Ant. spinothalamic (Pyramidal) Fasciculus gracilis Reticulospinal Reinnervation Ant. & Post. Tectospinal Axons regenerate and Spinocerebellar Rubrospinal reinnervate muscles Spinotectal Vestibulospinal Reformation of NMJ Spinoreticular Descending autonomic supported by perisynaptic Spino-olivary Schwann cells Remyelination of regenerated axons by Pyramidal tracts - conscious control of muscles Schwann cells (myelin from the cerebral cortex to the muscles of the sheath shorter and thinner than normal) body and face. (NB! PNS afferent All other tracts except the corticospinal are axons extrapyramidal tract. Extrapyramidal tracts are also regenerate but responsible for the unconscious reflexive or regenerated axons do not responsive control of musculature. regenerate into the CNS Tectospinal tract is concerned with reflex postural due la inhibitory movements in response to visual stimuli. molecules Vestibulospinal controls movement unconsciously at the CNS- PNS interface Descending autonomic are concerned with control of visceral activity Damage in descending autonomic will cause extrapyramidal symptoms BATCH 2028 1F 12  NEUROSCIENCE LC 2 CLASSIFICATION OF PERIPHERAL NERVE INJURY Multiple Sclerosis - the protective coating on the nerve fibers (myelin) is damaged and may eventually be destroyed. Depending on where the nerve damage occurs, MS can affect vision, sensation, coordination, movement, and bladder and bowel control. Figure 50. Seddon’s Classification of Nerve Injuries Figure 53. Signs and Symptoms of Multiple Sclerosis Refractory - no action potential Aphasia- language problem Brocca’s Aphasia - Difficulty in speaking but can comprehend Wernicke’s Aphasia - gibberish talk, can talk but difficulty in comprehension Figure 51. Schematic representation of the classification of peripheral nerve injury. Dysarthria - problems in the muscles in speech Dysphagia - problem in swallowing Conduction block - Problem with conduction Seddon classified peripheral nerve injury severity TABLE 6. NEURODEGENERATION. as class I (neuropraxia), class II (axonotmesis) or class III (neurotmesis), while first-to fifth-degree Regeneration of CNS Axonal regeneration is Nerve fibers (Tracts of possible in PNS classified by Sunderland axons) is not possible because: X. DEMYELINATION because: Axons in the CNS do not Connective tissue CLINICAL CORRELATION regenerate following injury. covering The destructive removal of myelin, an insulating In part, this is due to the fact can be sutured and protective fatty protein that sheaths nerve cell that CNS myelin contains (epineurium ) axons. several proteins When axons become demyelinated, they transmit that inhibit axonal regeneration. the nerve impulses 10 times slower than normal myelinated ones and in some cases they stop Absence of Endoneurium Presence of transmitting action potentials altogether. endoneurium There are a number of clinical diseases associated with the breakdown and destruction of Astrocytes deposit scar tissue Myelin sheath provides a the myelin sheath surrounding brain, spinal cord (Plaque) preventing tract along which or peripheral nerve axons cell growth regrowth occurs DEMYELINATING DISEASES Multiple sclerosis - Autoimmune Encephalomyelitis - Absence of neurilemma Presence of Neurilemma Neuromyelitis optica Transverse myelitis Oligodendrocytes do not Guillain Barre syndrome proliferate in response to Central pontine myelinolysis axonal injury Leukodystrophy Reference(s): Splittgerber, (2019). Snell’s Clinical Neuroanatomy (8th edition) Philadelphia: Wolters Kluwer Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., Figarella-Branger, D., Hawkins, C., Ng, H. K., Pfister, S. M., Reifenberger, G., Soffietti, R., & Ellison, D. W. (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro-Oncology, 23(8), 1231. https://doi.org/10.1093/neuonc/noab10 Figure 52. Axon of a nerve affected by MS BATCH 2028 1F 13