the injured brain Flashcards
what is a coup/countercoup injury?`
damage to brain resulting from
—> initial, sudden high velocity head movement i.e. coup
followed by
—> additional injury occurring in rebound movement i.e. countercoup
what are the different modes of axon damage?
what are two ways in which axons respond to damage?
MODES OF DAMAGE: • stretched axon • sheared axon • compressed axon • twisted axon
RESPONSE TO DAMAGE:
• disturbed ion balance = increased flow of fluid and ions = axon swelling = loss of conduction = loss of function
• Wallenium degeneration = axon separates = distal end of axon degrades
diffuse axonal injury:
- –> primary cause?
- –> secondary injury?
- –> biological changes?
primary cause:
• rapid tensile stretch of axons
secondary injury:
• damage to axonal cytoskeleton
• loss of elasticity
• axonal misallignment
biological changes:
• mechanical damage to sodium channels = massive sodium influx
—-> axonal swelling
—-> triggers calcium influx
—-> calcium activates proteolysis = further damage
what physical affects does DAI have on the brain?
- can cause haemorrhage due to axonal shearing
- can cause a midline shift due to axonal swelling
these affects reduce the network activity
epidural haemorrhage
- arterial injury to the middle meningeal artery
- normally associated with temporal bone or other skull fractures
- has a lenticular shape
- contained within dural sutures
- surgical emergency
subdural haemorrhage
- veinous injury to bridging veins
- typically caused by cortical injury —> skull fracture may not be present
- crescentic shape
- not contained by dural sutures but does not cross falx cerebri or tentorium cerebelli
• often seen in elderly individuals, trauma patients, and child abuse victims
—–> brain atrophy = tension on bridging veins and increased likelihood of rupture
subarachnoid haemorrhage
- blood in arachnoid spaces / hyperdensity in CSF
- caused by aneurysm rupture or post-traumatic superficial cortical contusions
- vasospasm several days after may cause secondary injruy
cerebral parenchymal haemorrhage
haemorrhage of small arterioles/capillaries in brain parenchyma
brain perfusion pressure (BPP) formula
brain perfusion pressure = mean arterial pressure - intracranial pressure
BPP = MAP - ICP
how is water homeostasis achieved in the brain
aquaporin-4 is main water channel in brain and is heavily involved in water homeostasis
AQP-4 facilitates drainage of CSF from arachnoid granulations to sinus spaces
on ventricle sides, AQP-4 used to pump water into CNS
what is a cytotoxic oedema?
swelling due to increased water intake
use an agonist of aquaporin 4 to pump out water and reduce swelling
what is a vasogenic oedema?
disruption of blood brain barrier causes water to leak into the brain
what is the glasgow coma scale and how does it work?
glasgow coma scale rates the:
1) eye opening
2) best verbal response
3) best motor response
a total GCS score is accumulated from these three categories and used to determine the severity of the injury
13-15 = mild TBI 9-12 = moderate TBI <9 = severe TBI
the lowest GCS score is observed in the first 48 hours of the injruy
what are the consequences of a CNS injury to motor and sensory tracts
when an injury happens to sensory/motor tracts, the area not connected to the cell body can not self sustain and degrades
motor: region below lesion cannot self sustain and dies
sensory: region above lesion cannot self sustain and dies
what are the management and repair strategies for CNS injury?
MANAGEMENT:
main goal is to preserve tissue
• preservation of neural tissue (close to site of impact)
• preservation of white matter (descending/ascending pathways)
REPAIR:
• replacement of lost cells
• regrow damaged pathways
• rewire circuitry appropriately
difference between flaccid paralysis and spasticity
flaccid paralysis:
• tone of the muscles is reduced and the muscles are weak
• damage to LMN (SC to muscles)
• reflexes suppressed
spasticity:
• muscles is raised and at the same time muscles are weak
• muscles are stiff and weak
• no cortical input i.e. damage to UMN (brain to SC)
• reflexes preserved
what are the primary and secondary injuries that result from CNS injury?
PRIMARY INJURY:
• mechanical i.e. force exerted onto brain/spinal cord
• immediate cell death and neural circuit disruption
SECONDARY INJURY: • mediated by primary injury • damaged by overexcitation • oedema and ischemia • inflammation ---> leads to further tissue damage/loss
what are the SCI outcomes of trauma-induced inflammation:
• anatomical & functional correlate?
• inflammatory cell infiltrate?
diagram :)
how does the complement system respond to injury?
BBB becomes disrupted after injury, allowing proteins to enter
proteins encounter a toxic environment of cell death and myelin debris —> activates complement system
C3 and C5 are central components of complement cascade
C5 —> MAC —> cell lysis
C3 —> C3b —> opsonisation
C3a/C5a —> engages cellular immune system = inflammatory response
how does diffusion tensor imaging (DTI) work?
magnetic pulse excites tissue for numerous directions
ISOTROPIC: in CSF + spinal grey matter —> water movement in any direction
ANISOTROPIC: in white matter —> water movement restricted to along axon —> restricted by axonal membranes and myelin
fractioonal anisotropy (FA): overall degree of diffusion directionality low FA = isotropic = grey matter = black high FA = anisotropic = white matter = white
what happens to fractional anisotropy (FA) after injury?
normal FA for white matter = ~0.8
white matter is mostly destroyed immediately after injury
this indicates a potential therapeutic window
what is IVIG?
intravenous immunoglobulin (IVIG) therapy
treatment for post-traumatic inflammation in SCI
IVIG is a liquid formulation containing purified immunoglobulin isolated from pooled blood plasma of >1,000 healthy donors
contains mostly IgG (>98%)
pushes towards “good side” of immunity i.e. repair not inflammation
already used clinically:
• antibody replacement therapy
• immunomodulatory agent in autoimmune disorders
what is BMS scoring?
what drug is administered to improve the BMS score?
BMS = basso mouse scale
functional assessment of locomotor performance in mice with SCI
ranges from 0-9
0 = total paralysis 9 = normal locomotion
IVIg dose of 0.5-1g/kg is acutely administered ----> results in highest improvement in locomotion • lesion volume reduced • scarring reduced • myelin increased • reduces the decrease of FA • reduces increase of radial diffusivity • reduces presence of macrophages • prevents complement activation
what is astrogliosis?
astrogliosis = accumulation of reactive astrocytes at and around the lesion core
- after CNS injury, widespread activation of astrocytes
- reactive astrocytes accumulate at the lesion border
- astrocytes forms wall = GLIAL SCAR
- segregates damaged from healthy tissue —> prevents spreading of injury
- barrier prevents axon regeneration
what is the “balance hypothesis” ?
balance hypothesis:
regeneration in the adult mammalian CNS is abortive due to imbalance of growth promoting/inhibiting factors
- an abundance of growth-inhibitory molecules
- a shortage in factors that support growth
what are the major restrictions of CNS regeneration?
- limited intrinsic potential (neurons)
- atrophy
- absence of an ‘aligned’ (glial) substrate
- neural scar and associated inhibitors
- lack of sufficient trophic support (balance hypothesis)
what is the OEG implant?
OEG implantation after SCI prevents secondary damage
lesion sites are reduced, but no axon regeneration
