CNS Response to Injury - Pathology - Revision history

Bara: Redirected page to Category:Central Nervous System - Response to Injury

2011-03-08T15:12:21Z

Redirected page to Category:Central Nervous System - Response to Injury

Bara: Redirected page to Category:CNS Response to Injury

2011-03-08T12:35:49Z

Redirected page to Category:CNS Response to Injury

Bara at 12:34, 8 March 2011

2011-03-08T12:34:49Z

Bara at 12:34, 8 March 2011

2011-03-08T12:34:17Z

Bara at 12:33, 8 March 2011

2011-03-08T12:33:43Z

Bara at 12:33, 8 March 2011

2011-03-08T12:33:12Z

Bara at 12:31, 8 March 2011

2011-03-08T12:31:53Z

Bara: Text replace - "[[Hindgut Fermenters - Horse - Anatomy & Physiology|" to "[[Equine Alimentary System - Anatomy & Physiology|"

2010-09-07T14:29:52Z

Text replace - "[[Hindgut Fermenters - Horse - Anatomy & Physiology|" to "[[Equine Alimentary System - Anatomy & Physiology|"

Karag7: /* Chromatolysis */

2009-08-28T09:01:22Z

Chromatolysis

Jtulloch at 08:45, 29 September 2008

2008-09-29T08:45:22Z

← Older revision		Revision as of 15:12, 8 March 2011
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−	#redirect[[:Category:~~CNS~~ Response to Injury]]	+	#redirect[[:Category:Central Nervous System - Response to Injury]]

← Older revision		Revision as of 12:35, 8 March 2011
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−	~~==Introduction==~~	+	#redirect[[:Category:CNS Response to Injury]]
−
−	* The CNS is composed of two major cell types:
−	*# Neurons
−	*# Glial cells, which include:
−	# Astrocytes
−	# Oligodendrocytes
−	# Microglial cells
−	# Ependymal cells
−	# Choroid plexus epithelial cells
−	* The response to injury varies with the cell type injured.
−
−	==[[~~Neuron~~ Response to Injury]]==
−
−
−	~~==[[Glial Cell Response to Injury]]==~~
−
−
−
−	~~==[[General CNS Responses to Injury]]==~~
−
−
−
−	~~==[[Excitotoxicity]]==~~

← Older revision		Revision as of 12:34, 8 March 2011
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	==[[Excitotoxicity]]==		==[[Excitotoxicity]]==
−
−	* The term "excitotoxicity" is used to describe the process by which neurons are damaged by glutamate and other similar substances.
−	* Excitotoxicity results from the overactivation of excitatory receptor activation.
−
−	~~===The Mechanism of Excitotoxicity===~~
−
−	* '''Glutamate''' is the major excitatory transmitter in the brain and spinal cord.
−	** There are four classes of postsynaptic glutamate receptors for glutamate.
−	*** The receptors are either:
−	**** Directly or indirectly associated with gated ion channels, '''OR'''
−	**** Activators of second messenger systems that result in release of calcium from intracellular stores.
−	*** The receptors are named according to their phamacological agonists:
−	**** '''NMDA receptor'''
−	***** The NMDA receptor is directly linked to a gated ion channel.
−	***** The ion channel is permeable to Ca<sup>++</sup>, as well as Na<sup>+</sup> and K<sup>+</sup>.
−	***** The channel is also voltage dependent.
−	****** It is blocked in the resting state by extracellular Mg<sup>++</sup>, which is removed when membrane is depolarised.
−	***** I.e. both glutamate and depolarisation are needed to open the channel.
−	**** '''AMPA receptor'''
−	***** The AMPA receptor is directly linked to a gated ion channel.
−	***** The channel is permeable to Na<sup>+</sup> and K<sup>+</sup> but NOT to divalent cations.
−	***** The receptor binds the glutamate agonist, AMPA, but is not affected by NMDA.
−	***** The receptor probably underlies fast excitatory transmission at glutamatergic synapses.
−	**** '''Kainate receptor'''
−	***** Kainate receptors work in the same way as AMPA receptors, and also contribute to fast excitatory transmission.
−	**** '''mGluR''', the '''metabotropic receptor'''
−	***** Metabotropic receptors are indirectly linked to a channel permeable to Na<sup>+</sup> and K<sup>+</sup>.
−	***** They also activate a phoshoinositide-linked second messenger system, leading to mobilisation of intra-cellular Ca<sup>++</sup> stores.
−	***** The physiological role ot mGluR is not understood.
−
−	* Under normal circumstances, a series of glutamate transporters rapidly clear glutamate from the extracellular space.
−	** Some of these transporters are neuronal; others are found on astrocytes.
−	* This normal homeostatic mechanism fails under a variety of conditions, such as ischaemia and glucose deprivation.
−	** This results in a rise in extracellular glutamate, causing activation of the neuronal glutamate receptors.
−	* Two distinct events of excitiotoxicity arise from glutamate receptor activation:
−	*# The depolarisation caused mediates an influx of Na<sup>+</sup>, Cl<sup>-</sup> and water. This give '''acute neuronal swelling''', which is reversible.
−	*# There is a '''rise in intracellular Ca<sup>++</sup>'''.
−	# This is due to:
−	#* Excessive direct Ca<sup>++</sup> influx via the NMDA receptor-linked channels
−	#* Ca<sup>++</sup> influx through voltage gated calcium channels following depolarisation of the neuron via non-NDMA receptors
−	#* Release of Ca<sup>++</sup> from intracellular stores.
−	# The rise in neuronal intracellular Ca<sup>2+</sup> serves to:
−	#* Uncouple mitochondrial electron transport and activate nitric oxide synthase and phospholipase A, leading to generation of reactive oxygen and nitrogen species which damage the neurone.
−	#* Activats a number of enzymes, including phospholipases, endonucleases, and proteases.
−	#** These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.
−	* Excitotoxicity is, therefore, a cause of acute neuron death.
−
−
−	~~[[Category:CNS Response to Injury]]~~

← Older revision		Revision as of 12:34, 8 March 2011
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	==[[General CNS Responses to Injury]]==		==[[General CNS Responses to Injury]]==

−	~~===Ischaemic Damage===~~
−
−	* The CNS is particularly sensitive to ischaemia, because it has few energy reserves.
−	* The CNS is protected by its bony covering.
−	** Despite offering protection, the covering also makes the CNS vulnerable to certain types of damage, for example:
−	*** Damage due to fractures and dislocation.
−	*** Damage due to raised intracranial pressure.
−	**** Raised intracranial stimulates a compensatory increase in blood flow, further raising intracranial pressure. This stimulates a further increase in blood flow, and the cycle continues until intracranial pressure is so high that blood flow is impeded.
−	***** The result of this is '''ischaemia'''.
−	* Survival of any cell is dependent on having sufficient energy.
−	** Ischaemia causes cell death by impeding energy supply to cells.
−	*** Cells directly affected by ischamia die rapidly.
−	**** For example, those suffering a failure of pefusion due to an infarct.
−	*** Neurons surrounding this area of complete and rapid cell death exist under sub-optimal conditions and die over a more prolonged period.
−	**** This area of gradual death is known as the '''lesion penumbra'''.
−	**** There are several mechanisms implicated in cell death in the penumbra:
−	****# Increase in intracellular calcium
−	****# Failure to control free radicals
−	****# Generation of nitrogen species (e.g NO and ONOO) are the main damaging events.
−
−	~~===Oedema===~~
−
−	* There are three types of cerebral oedema:
−	*# '''Vasogenic oedema'''
−	# Vasogenic oedema follows vascular injury.
−	# Oedema fluid gathers outside of the cell.
−	# This is the most common variation of cerebral oedema.
−	*# '''Cytotoxic oedema'''
−	# Cytotoxic oedema is due to an energy deficit.
−	#* The neuron can’t pump out sodium and water leading to swelling within the cell.
−	*# '''Interstitial oedema'''
−	# Associated with hydrocephalus.
−	# This type of cerebral oedema is of lesser importance.
−	* One serious consequence of oedema is that the increase in size leads to the brain trying to escape the skull.
−	** This causes herniation of the brain tissue.
−	** The most common site of herniation is at the foramen magnum.
−	*** The medulla is compressed at the site of the respiratory centres, leading to death.
−
−	~~===Demyelination===~~
−
−	* Demyelination is the loss of initially normal myelin from the axon.
−	* Demyelination may be primary or secondary.
−
−	~~====Primary Demyelination====~~
−
−	* Normally formed myelin is selectively destroyed; however, the axon remains intact.
−	* Causes of primary demyelination:
−	** Toxins, such as hexachlorophene or triethyl tin.
−	** Oedema
−	** Immune-mediated demyelination
−	** Infectious diseases, for example canine distemper or caprine arthritis/encephalitis.
−
−	~~====Secondary Demyelination====~~
−
−	* Myelin is lost following damage to the axon.
−	** I.e. in [[CNS Response to Injury - Pathology#Wallerian Degeneration\|wallerian degeneration]]
−
−	~~===Vascular Diseases===~~
−
−	* Vascular diseases can lead to complete or partial blockage of blood flow which leads to ischaemia.
−	** Consequences of ischaemia depend on:
−	**# Duration and degree of ischaemia
−	**# Size and type of vessel involved
−	**# Susceptibility of the tissue to hypoxia
−	* Potential outcomes of vascular blockage include:
−	** Infarct, and
−	** Necrosis of tissue following obstruction of its blood supply.
−	* Causes include:
−	** Thrombosis
−	*** Uncommon in animals but may be seen with DIC or sepsis.
−	** Embolism. e.g.
−	*** Bone marrow emboli following trauma or fractures in dogs
−	*** Fibrocartilaginous embolic myelopathy
−	** Vasculitis, e.g.
−	*** Hog cholera (pestivirus)
−	*** Malignant catarrhal fever (herpesvirus)
−	*** Oedema disease (angiopathy caused by E.coli toxin)
−
−	~~===Malacia===~~
−
−	* Malacia may be used:
−	** As a gross term, meaning "softening"
−	** As a microscopic term, meaning "necrosis"
−	* Malacia occurs in:
−	** Infarcted tissue
−	** Vascular injury, for example vasculitis.
−	** Reduced blood flow or hypoxia, e.g.
−	*** Carbon monoxide poisoning, which alters hemoglobin function
−	*** Cyanide poisoning, which inhibits tissue respiration
−
−
−	~~[[Category:CNS Response to Injury]]~~

← Older revision		Revision as of 12:33, 8 March 2011
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	==[[Glial Cell Response to Injury]]==		==[[Glial Cell Response to Injury]]==

−	* The order of susceptibility of CNS cells to injury runs, from most to least susceptible:
−	*# Neurons
−	*# Oligodendroglia
−	*# Astrocytes
−	*# Microglia
−	*# Endothelial cells
−
−	~~===Astrocytes===~~
−
−	* The response of astrocytes to insult include:
−	** '''Necrosis'''
−	** '''Astrocytosis'''
−	*** An increase in the number of astrocytes (i.e. astrocyte hyperplasia).
−	** '''Astrogliosis'''
−	*** An increase in the size of astrocytes (i.e. astrocyte hypertrophy).
−	** '''Gliosis'''
−	*** Formation of glial fibres.
−	*** This is a form of scarring in the CNS.
−
−	~~===Oligodendrocytes===~~
−
−	* Oligodendrocytes are prone to hypoxia and degeneration
−	* Oligodendrocytes proliferate around damaged neurons.
−	** This is known as '''satellitosis'''.
−	* Death of oligodendrocytes causes demyelination.
−
−	~~===Microglial Cells===~~
−
−	* Microglial cells can respond in two ways to CNS injury.
−	*# They may phagocytose cell debris to transform to gitter cells.
−	# Gitter cells are large macrophages with foamy cytoplasm. [http://w3.vet.cornell.edu/nst/nst.asp?Fun=F_KSsrch&kw=GITTER View images courtesy of Cornell Veterinary Medicine]
−	*# They may form glial nodules.
−	# These are small nodules that occur notably in viral diseases.
−
−
−	~~[[Category:CNS Response to Injury]]~~

← Older revision		Revision as of 12:33, 8 March 2011
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	==[[Neuron Response to Injury]]==		==[[Neuron Response to Injury]]==

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

	==[[Glial Cell Response to Injury]]==		==[[Glial Cell Response to Injury]]==

@@ Line 1: / Line 1: @@
 ==Introduction==
@@ Line 20: / Line 10: @@
 *#* Choroid plexus epithelial cells
 * The response to injury varies with the cell type injured.
-−
-==Response of Neurons to Injury==
+==[[Neuron Response to Injury]]==
 * Neurons are particularly vulnerable to injury, due to their:
@@ Line 131: / Line 121: @@
 ** It may sometimes be a normal feature.
 ==Glial Cell Response to Injury==
 * The order of susceptibility of CNS cells to injury runs, from most to least susceptible:
@@ Line 167: / Line 160: @@
 *#* These are small nodules that occur notably in viral diseases.
 ==General Responses to Injury==
 ===Ischaemic Damage===
@@ Line 259: / Line 256: @@
 *** Cyanide poisoning, which inhibits tissue respiration
 ==Excitotoxicity==
 * The term "excitotoxicity" is used to describe the process by which neurons are damaged by glutamate and other similar substances.
@@ Line 306: / Line 307: @@
 *#*** These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.
 * Excitotoxicity is, therefore, a cause of acute neuron death.

@@ Line 78: / Line 78: @@
 ** It is an adaptive response to deal with the injury.
 ** It can, however lead to necrosis.
-* Seen, for example, in grass sickness in [[Hindgut Fermenters - Horse - Anatomy & Physiology|horses]] (equine dysautonomia).
+* Seen, for example, in grass sickness in [[Equine Alimentary System  - Anatomy & Physiology|horses]] (equine dysautonomia).
 [http://w3.vet.cornell.edu/nst/nst.asp?Fun=Display&imgID=13353 View images courtesy of Cornell Veterinary Medicine]

@@ Line 73: / Line 73: @@
 * Chromatolysis is the cell body’s reaction to axonal insult.
-* The cell body swells and the Nissl substance disperses.
+* The cell body swells and the Nissl substance (granular cytoplasmic reticulum and ribosomes found in nerve cell bodies) disperses.
 ** Dispersal of the Nissl substance allows the cell body to produce proteins for rebuilding the axon.
 * IT IS NOT A FORM OF NECROSIS.

← Older revision		Revision as of 08:45, 29 September 2008
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