What is CNS trauma?
Acute - traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), due to a physical insult to the CNS.
Chronic - degenerative disease - alzheimers, parkinsons.
What are examples of acute CNS trauma?
Closed head injury - concussion.
Blast-induced TBI
Stroke
Nerve agents
Neurotoxins
What are examples of chronic CNS trauma?
Brain tumours
Parkinson’s
Alzheimers
ALS
Huntingdon’s
Alcohol abuse
Drug abuse
Glaucoma
What is glaucoma?
Degeneration of the optic nerve, which originates from the retina - a thin layer of cells on the back of the eye.
First lose peripheral vision, then as lose more cells in the retina, the vision deteriorates until you go blind.
What is the mechanism of CNS trauma?
Acute or chronic insults cause pathophysiological changes - cerebral oedema, inflammation, cytotoxicity, loss of cerebral autoregulation, apoptosis.
This causes secondary neuronal damage in the limbic system, basal ganglia, brain stem, forebrain, cerebellum and cerebral cortex.
What are the neuropsychiatric disorders that can arise from CNS trauma?
Memory and cognitive deficits.
Sleep disruptions
Mental and emotional symptoms
Impaired psychomotor and neuromotor functions.
What is the common feature of CNS injuries?
They are diverse disorders, but all have severe detrimental effects.
This is because the CNS neurones do not regenerate, there is limited capacity for repair. Neuronal loss and cell death results in permanent functional cell death.
What prevents CNS regeneration?
Injury response - creates inhibitory environments, there is a lack of trophic support, and cells are lost due to cell death mechanism.
What is the neuronal response to mechanical insult?
The primary damage causes a breakdown of the blood brain barrier or spinal barrier which leads to necrosis.
This causes the CNS to activate the glial response, which causes phagocytosis to remove the neuronal debris, reduces excitotoxicity and separates the injury site.
But this forms a long-term glial scar, which inhibits neurite outgrowth and regeneration.
What is the neuronal response to secondary damage caused by primary damage from mechanical insult?
Primary damage causes inflammation, excitotoxicity, ischaemia, free radicals, oedema and apoptosis.
This again activates the initial glial response, which also creates the inhibitory scar environment.
It also has repair attempts - cells start neurogenesis, which is ineffective, angiogenesis - sprouting new blood vessels, and increase in beneficial ECM proteins.
What is the glial scar?
The inflammatory cells interact with reactive glial cells - astrocytes, which seal of the blood brain barrier, to retain tissue integrity and reduce the inflammatory response by forming scars.
But scarring is associated with upregulation of inhibitory molecules and ECM deposition due to dysregulation of ECM turnover.
What is the consequence of the glial scar?
The injured CNS is non-permissive for axonal regeneration, but there are regeneration mechanisms, but these fail so dystrophic neurones develop.
Why is regeneration possible in the PNS?
The axons are myelinated by Schwann cells, which creates a permissive environment for axons and nerves to grow.
They allow longitudinal alignment and release growth promoter factors for regeneration.
The neurones can reform the sheath.
How does the PNS and CNS environment differ?
The PNS nerves are mostly white matter, so there are no cell bodies.
The CNS nerves have grey matter in the middle, and white matter on the outside. The grey matter contains cell bodies.
The PNS signals into the sensory areas of grey matter, and then the CNS signals from the motor areas of the grey matter into the PNS.
What happens when a PNS nerve is injured by crush injury?
The axon is damaged and broke, the axon tissue decays back to the first Schwann cell - the node of Ranvier.
The Schwann cells break away and accumulate around the debris of nerves to clear it, and signal to macrophages in blood to clear it.
The Schwann cells change phenotype and line up in a band.
Sprouting axons are directed towards the distal part of the nerve.
Distal axons are degenerating, but proximal axons sense the chemical trace and regenerate it.
The Schwann cells then myelinate the new axons.
What happens when a PNS nerve is injured by a clean cut?
Lots of the tissue is lost so the Schwann cells cannot line up, so the sprouting axons have no direction, and become a neuroma.
The axons don’t reconnect to the distal part of the nerve, so motor function and sensations are lost in this area.
What happens when a CNS nerve is injured?
The axons degenerate.
Oligodendrocytes die, some clear the debris but inefficiently, and microglia also do not clear the debris.
The grey matter is full of other neuronal cell bodies, fibroblasts, astrocytes and other cell bodies, so the sprouting axons cannot reach the distal part.
The astrocytes lay down scar tissue, which the axons cannot go through.
Why do oligodendrocytes mean regeneration is not possible in the CNS?
Oligodendrocytes are the CNS myelinating cells, they do not form a guidance part for sprouting axons.
The oligodendrocytes release inhibitory molecules.
How does the PNS and CNS environment differ?
The PNS nerves are mostly white matter, so there are no cell bodies.
The CNS nerves have grey matter in the middle, and white matter on the outside. The grey matter contains cell bodies.
The PNS signals into the sensory areas of grey matter, and then the CNS signals from the motor areas of the grey matter into the PNS.
Why do astrocytes mean that regeneration is not possible in the CNS?
Astrocytes release factors that promote glial scar deposition, which is inhibitory.
Release Chondroitin sulfate proteoglycans (CSPGs) molecules which are inhibitory
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Voltage-gated ion channels42
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Ionotropic receptors and synapses50
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Metabotropic receptors and Neuromodulation36
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Computer practical26
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Anatomy of motor systems44
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Motor control 134
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Motor control 2 - basal ganglia44
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Learning and memory33
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Pain35
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Limbic system20
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Drug dependence33
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Anxiety and depression36
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Schizophrenia29
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Neurotrauma20
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Neurodegeneration31
