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Components of Central Nervous System (CNS) Neurons, Glia: gray matter, white matter Neuropil (nerve fibers + glia processes) Synapse Glia (Neuroglia) Astrocyte (Astroglia) Microglia Oligodendrocyte (Oligodendroglia) Ependyma (choroid plexus epithelium) Histo: CNS - 1 Components: Neurons, Glia and Neuropil Gray matter: Neurons (+ processes), Glia White matter: Nerve fibers (processes), Glia Neuropil: nerve processes + glia processes Neuropil Histo: CNS - 2 Synapses Functional classifications Chemical synapse Neurotransmitters, Neuropeptides Electronic synapse: gap junction (nexus), connexin Morphological classification (EM) Histo: CNS - 3 Chemical Synapses Ultrastructures Presynaptic element: synaptic vesicles Synaptic cleft Postsynaptic element: clustering of receptors/channels Neurotransmitters acetylcholine (ACh), noradrenaline (NE), gamma-aminobutyric acid (GABA), serotonin (5-HT), dopamine (DA), glycine, glutamate, aspartate etc. Neuropeptides (peptidergic): calcitonin gene-related peptide (CGRP), etc. Histo: CNS - 4 Structural classification of Synapses axosomatic synapse axodendritic synapse axoaxonic synapse Axosomatic Axodendritic Axoaxonic Histo: CNS - 5 Neuroglia Microglia (macrophage) Histo: CNS - 6 Neuroglia Non-nervous elements; more abundant than neurons protective, supportive, nutritive Exist in the extraneuronal space as ionic sink little true tissue space, no lymphatics Proliferate in CNS injury Histo: CNS - 7 Types of neuroglia Astrocytes (Astroglia) Protoplasmic, Fibrous Oligodendrocytes (Oligodendroglia) Microglia (Mesoglia) Ependyma cells, Choroid epithelium Histo: CNS - 8 Astrocytes Perivascular feet (Foot plates) “glia limitans” (LM) on brain surface subpia foot of astrocytes basal lamina of pia matter (EM) cytoplasm: glial fibrillary acidic protein (GFAP) ?Functions: barriers, metabolism Histo: CNS - 9 Protoplasmic astrocytes in gray matter Stellate form with multiple radiating processes A larger and paler nucleus than other glial cells Processes ending as vascular feet/pedicles (perivascular feet) and perineural feet Histo: CNS - 10 Protoplasmic astrocyte Blood vessel Cajal method Silver impregnation GFAP Histo: CNS - 11 Fibrous astrocytes in white matter, and periventricular gray matter an ovoid euchromatic nucleus with pale-staining cytoplasm and long, thin processes Histo: CNS - 12 Fibrous astrocyte Immunocytochemistry GFAP Silver-gold impregnation Histo: CNS - 13 Microglia Mononuclear phagocytic cells A dense oval or elongate nucleus with scant cytoplasm Tortuous processes with spines Upon injury: proliferate, loose spines, become swollen (“amoeboid”) Histo: CNS - 14 Microglia Microgliosis Silver impregnation Immunohistochemistry: MHCII (major histocompatibility complex II) for activated microglia Histo: CNS - 15 Oligodendrocytes Form myelin sheath in CNS Smaller size than astrocytes Small irregularly shaped deeply stained nucleus Various classifications and Types Perineural oligodendrocytes Perifascicular oligodendrocytes Histo: CNS - 16 Perineuronal oligodendrocytes Mainly in gray matter Closely associated with soma of neurons ? Functions: metabolic interdependency oligo Histo: CNS - 17 Perifascicular oligodendrocytes Mainly in white matter arranged in rows between bundles of axons Analogous to Schwann cells in PNS forming myelin sheaths of several parallel axons, up to 50 or more Histo: CNS - 18 Oligodendrocytes Perineuronal oligodendrocytes Perifascicular oligodendrocytes 19 Histo: CNS - 19 Different patterns of myelination between CNS and PNS: 1/3 1. Surface of the node: contacted by astrocyte processes in CNS; covered by Schwann cell processes in PNS. 2. Cytoplasm of myelinating cells near the node of Ranvier: (-) for Oligo; (+) for Schwann cells. Histo: CNS - 20 Different patterns of myelination between CNS and PNS: 2/3 3. One Oligo for several axons; One Schwann for a single axon 4. Distance between cell body and myelin sheath: Oligo > Schwann Histo: CNS - 21 Different patterns of myelination between CNS and PNS: 3/3 5. Basal lamina associated with myelin sheath: (-) in CNS, (+) in PNS 6. Supporting connective tissue for myelinated axons: (-) in CNS, (+) in PNS Histo: CNS - 22 Demyelinating diseases Myelin proteins only in PNS: peripheral myelin protein 22 (PMP22) etc only in CNS: proteolipid protein (PLP) etc. in PNS and CNS: myelin-associated glycoprotein (MAG) etc. Demyelinating diseases PNS: Guillain-Barré syndrome (acute inflammatory demyelinating polyradiculopathy) 急性神經根炎 CNS: multiple sclerosis 多發性硬化症 Histo: CNS - 23 Guillain-Barré syndrome (GBS) Progressive Day 1 weakness Lower limbs Day 3 Upper limbs Day 7 Respiratory failure Histo: CNS - 24 Ependymal cells Lining cells of ventricular system Ventricles Aqueduct Central canal Choroid plexus: continuous with ependyma cells of ventricles Histo: CNS - 25 Ependymal cells Histo: CNS - 26 Ependymal cells C: cilia M:microvilli JC: junctional complex BB: basal body G: Golgi apparatus Histo: CNS - 27 Choroid plexus Ependyma layer + vascular core (fenestrated vessels + loose connective tissues) Produce cerebrospinal fluid (CSF) Histo: CNS - 28 Blood-Brain Barrier (BBB) Nonfenestrated (continuous type) endothelial cells (tight junctions) thick basal lamina with outer surfaces enclosed by Astrocyte foot processes (perivascular feet, end feet) Histo: CNS - 29 Blood-Brain Barrier Capillary of continuous type; Thick basal lamina; Perivascular feet Functions: impermeable to foreign substances for preventing Autoimmune damage Blood vessel Histo: CNS - 30 Meninges Dural mater (pachymeninx) periosteum of skull subdural space Pia-arachnoid (leptomenginges) Arachnoid mater subarachnoid space / cistern Intact vessels Pia mater Histo: CNS - 31 Meninges Histo: CNS - 32 Pia-Arachnoid Histo: CNS - 33 Organization of CNS Cerebellum: 3 layers Cerebral cortex (Neocortex): 6 layers (cytoarchitecture: Broadmann area) Histo: CNS - 34 Mol: molecular layer Pkj: Purkinje cell layer Gr: granular layer Cerebellum Cerebellar cortex Histo: CNS - 35 Pyramidal cells (neurons) Histo: CNS - 36 Cerebral cortex (Neocortex): 6 layers 1. Plexiform (molecular) layer 2. Outer granular layer 3. Pyramidal cell layer 4. Inner granular layer 5. Ganglionic layer 6. Multiform cell layer White matter Histo: CNS - 37 Response of a nerve to injury Histo: CNS - 38 Nerve Degeneration and Regeneration Histo: CNS - 39 Nerve injury: PNS vs. CNS Histo: CNS - 40 Nerve Degeneration and Regeneration Wallerian degeneration: disintegration of axonal cytoskeleton distal to the site of injury Cell body: chromatolysis (loss of Nissl substance) Responses PNS: proliferation of Schwann cells; migration of macrophage CNS: proliferation of astrocytes Regeneration PNS: as a rule CNS: negligible inhibitory molecules, glial scar etc. Histo: CNS - 41 Review of CNS Histology Components of CNS: neurons, glia Neurons, Glia: gray matter, white matter Neuropil (nerve fibers + glia processes) Synapse Glia (Neuroglia) Meninges (Menix) Blood-Brain Barrier Organization of the CNS: layers Responses to nerve injury Histo: CNS - 42