LECTURE 25 - CNS response to trauma Flashcards
What is CNS trauma?
Acute
- TBI and traumatic spinal cord injury (SCI) can be result of a physical insult to the CNS e.g. road accidents, strokes, neurotoxins
Chronic
- degenerative disease -AlzD, PD etc., brain tumours, ALS, alcohol and drug abuse
What pathophysiological changes can occur from both chronic and acute insults?
- cerebral oedema
- inflammation
- cytotoxicity
- loss of cerebral auto regulation
- apoptosis
What damage can occur after pathophysiological changes?
Secondary neuronal damage in the:
- limbic system
- basal ganglia
- brain stem
- forebrain
- cerebellum
- cerebral cortex
What neuropsychiatric disorders can arise after secondary neuronal damage?
- memory/cognitive deficits
- sleep disruptions
- mental and emotional symptoms
- impaired psychomotor and neuromotor functions
What is common feature of all CNS injuries?
- leads to severe detrimental effefcts
- mammalian CNS does not regenerate, has a limited capacity for repair, neuronal loss and cell death results in permanent functional cell death
How are injuries to the spinal cord split up?
- C4 injury
- C6 injury
- T6 injury
- L1 injury
What is a C4 injury?
- Quadriplegia/ Tetraplegia
- results in complete paralysis below the neck
What is a C6 injury?
- results in partial paralysis of hands and arms as well as lower body
What is a T6 injury?
- Paraplegia
- results in paralysis below the chest
What is an L1 injury?
- Paraplegia
- results in paralysis below the waist
How prevalent are TBIs and SCIs?
TBI
- over 1M people in UK living with TBI
- in 2016-2017, there were 348,453 UK admissions with brain injury and 155,919 for head injury
- men are 1.5x more likely to be admitted for head injury
SCI
- more than 50,000 people in UK and Ireland living with paralysis caused by SCI
- every day, 3 people are told they will never walk again
- more than 2.5 million worldwide live with paralysis caused by SCI
What are the consequences of CNS injury?
- functional deficits
- CNS neurones do not regenerate
What prevents regeneration of CNS neurones? - injury response
- inhibitory environments (characterised by glial scar and up-regulation of inhibitory molecules such as CSPG, MAG and Nogo-A)
- lack of trophic support
- loss of cells
What are the mechanisms of damage and inhibition of regeneration as we’ll as the permissive and reparative mechanisms?
Mechanical insult
–>
Primary damage: mechanical failure; BBB/BSCB breakdown, necrosis
–> (EITHER)
Secondary damage: inflammation, excitotoxicity, ischemia, free radicals, oedema, apoptosis
WHICH LEADS TO
- repair attempts; increased neurogenesis, angiogenesis (blood vessel formation), increase in beneficial ECM proteins (extracellular matrix) - helps cells move around
–> (OR (reparative))
initial glial response; phagocytosis; decreased excitotoxicity, sequester injury site
WHICH LEADS TO
long-term glial scar; inhibits neurone outgrowth/regeneration
ALL OCCURS ALONGSIDE EACH OTHER
What happens when the blood brain barrier (BBB) breaks down?
- -> lesion cavity expands due to inflammation
- -> inflammatory cells interact with reactive glial cells
- -> reactive astrocytes seal off the BBB
- -> to retain tissue integrity and reduce the inflammatory response (scar formation)
- scarring is associated with upregualtion of inhibitory molecules and ECM deposition
- injured CNS is non-permissive for axonal regeneration and dystrophic neurones develop
What cellular interactions does CNS injury response lead to?
- dystrophic neurones
- severed axons and axonal sprouting
- highly active structures which are stalled without functional growth
- neuronal death
- lack of neurotrophic support (cells lack nutrients to stay alive)
- production of inhibitory molecules (oligos/myelin)
- demyelination
- glial scar - barrier to regeneration
