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| | ==[[Neuron Response to Injury]]== | | ==[[Neuron Response to Injury]]== |
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| − | * Neurons are particularly vulnerable to injury, due to their:
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| − | ** High metabolic rate
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| − | ** Small capacity to store energy
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| − | ** Lack of regenerative ability
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| − | ** Axons being very dependent on the cell body.
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| − | *** Axons cannot make their own protein as they have no Nissl substance.
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| − | *** The cell body produces the axon's protein and disposes of its waste.
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| − | *** Death or damage of the cell body causes axon degeneration.
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| − | * There are four ways in which neurons may react to insult:
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| − | *# Acute Necrosis
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| − | *# Chromatolysis
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| − | *# Wallerian Degeneration
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| − | *# Vacuolation
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| − | ===Acute Necrosis===
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| − | * Acute necrosis is the most common neuronal response to injury.
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| − | * Causes of actue necrosis include:
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| − | ** Ischaemia
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| − | *** Diminution of the blood supply causes a lack of nutrients and oxygen, inhibiting energy production. A decrease in the levels of ATP leads to:
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| − | ***# Failure of the Na<sup>+</sup>/K<sup>+</sup>pumps, causing cell swelling and an increase in extracellular potassium.
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| − | ***# Failure to generate NAD required for DNA repair.
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| − | ** Hypoxia
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| − | ** Hypoglycaemia
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| − | ** Toxins, such as lead and mercury
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| − | ====Laminar Cortical Necrosis====
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| − | * Laminar cortical necrosis refers to the selective destruction of neurons in the deeper layers of the cerebral cortex.
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| − | ** These neurons are the most sensitive to hypoxia.
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| − | * The laminar cortical pattern of acute necrosis occurs in several instances:
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| − | *# Ischaemia
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| − | *#* For example, seizure-related ischaemia in dogs.
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| − | *# Polioencephalomalacia in ruminants
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| − | *#* Also called cerebrocortical necrosis or CCN.
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| − | *# Salt poisoning in swine
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| − | *# Lead poisoning in cattle
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| − | * It is most likely that gross changes will not be seen. When they are visible, changes may be apparent as:
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| − | ** Oedema
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| − | *** Causes brain swelling, flattened gyri and herniation
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| − | ** A thin, white, glistening line along the middle of the cortex.
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| − | *** In ruminants, this fluoresces with UV-light.
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| − | * Ultimately the cortex becomes necrotic and collapses.
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| − | [http://w3.vet.cornell.edu/nst/nst.asp?Fun=F_KSsrch&kw=POLIOENCEPHALOMALACIA View images courtesy of Cornell Veterinary Medicine]
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| − | ===Chromatolysis===
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| − | * Chromatolysis is the cell body’s reaction to axonal insult.
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| − | * The cell body swells and the Nissl substance (granular cytoplasmic reticulum and ribosomes found in nerve cell bodies) disperses.
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| − | ** Dispersal of the Nissl substance allows the cell body to produce proteins for rebuilding the axon.
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| − | * IT IS NOT A FORM OF NECROSIS.
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| − | ** It is an adaptive response to deal with the injury.
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| − | ** It can, however lead to necrosis.
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| − | * Seen, for example, in grass sickness in [[Equine Alimentary System - Anatomy & Physiology|horses]] (equine dysautonomia).
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| − | [http://w3.vet.cornell.edu/nst/nst.asp?Fun=Display&imgID=13353 View images courtesy of Cornell Veterinary Medicine]
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| − |
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| − | ===Wallerian Degeneration===
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| − | * Wallerian degeneration is the axon’s reaction to insult.
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| − | * The axon and its myelin sheath degenerates distal to the point of injury.
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| − | * There are several causes of wallerian degeneration:
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| − | ** Axonal transection
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| − | *** This is the "classic" cause
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| − | ** Vascular causes
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| − | ** Inflamatory reactions
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| − | ** Toxic insult
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| − | ** As a sequel to neuronal cell death.
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| − | [http://w3.vet.cornell.edu/nst/nst.asp?Fun=F_KSsrch&kw=WALLERIAN View images courtesy of Cornell Veterinary Medicine]
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| − | ====The Process of Wallerian Degeneration====
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| − | # '''Axonal Degeneration'''
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| − | #* Axonal injuries initially lead to acute axonal degeneration.
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| − | #** The proximal and distal ends separate within 30 minutes of injury.
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| − | #* Degeneration and swelling of the axolemma eventually leads to formation of bead-like particles.
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| − | #* After the membrane is degraded, the organelles and cytoskeleton disintegrate.
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| − | #** Larger axons require longer time for cytoskeleton degradation and thus take a longer time to degenerate.
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| − | # '''Myelin Clearance'''
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| − | #* Following axonal degeneration, myelin debris is cleared by phagocytosis.
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| − | #* Myelin clearance in the PNS is much faster and efficient that in the CNS. This is due to:
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| − | #** The actions of schwann cells in the PNS.
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| − | #** Differences in changes in the blood-brain barrier in each system.
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| − | #*** In the PNS, the permeability increases throughout the distal stump.
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| − | #*** Barrier disruption in CNS is limited to the site of injury.
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| − | # '''Regeneration''' [[Image:neuronalvacuolation1.jpg|thumb|right|150px|Neuronal vacuolation. Image courtesy of BioMed Archive]]
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| − | #* Regeneration is rapid in the PNS.
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| − | #** Schwann cells release growth factors to support regeneration.
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| − | #* CNS regeneration is much slower, and is almost absent in most species.
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| − | #** This is due to:
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| − | #*** Slow or absent phagocytosis
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| − | #*** Little or no axonal regeneration, because:
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| − | #**** Oligodendrocytes have little capacity for remyelination compared to Schwann cells.
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| − | #**** There is no basal lamina scaffold to support a new axonal sprout.
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| − | #**** The debris from central myelin inhibits axonal sprouting.
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| − | ===Vacuolation===
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| − | [[Image:neuronalvacuolation2.jpg|thumb|right|150px|Neuronal vacuolation. Image courtesy of BioMed Archive]]
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| − | * Vacuolation is the hallmark of transmissible spongiform encephalopathies.
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| − | ** For example, BSE and Scrapie.
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| − | * Vacuolation can also occur under other circumstances:
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| − | ** Artefact of fixation
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| − | ** Toxicoses
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| − | ** It may sometimes be a normal feature.
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| − | [[Category:CNS Response to Injury]]
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| | ==[[Glial Cell Response to Injury]]== | | ==[[Glial Cell Response to Injury]]== |