TBI Flashcards
traumatic brain injury TBI
occurs when an insult to the brain from an external mechanical force causes the brain to move rapidly within the skull, leading to damage
TBI can be an impact event
head makes direct contact with an object
TBI can be a nonimpact event
head encounters a force such as blast waves or rapid acceleration/deceleration
is TBI higher in men or women?
men
leading cause of TBI?
falls
more than 2/3 of TBI cases are
milk (aka concussions)
the brain is naturally protected from injury - the skull
a natural helmet that absorbed impacts & protects
Severity of TBI can be divided into 4 categories
subclinical, mild, moderate, severe
TBI can lead to - changes in
molecular signaling
TBI can lead to - alteration in cellular
structure/function
TBI can lead to what type of injury
primary tissue injury
TBI can lead to BBB
dysfunction
2 phases of TBI
acute primary injury
delayed, secondary injury
1st phase - acute primary injury
mechanical forces disrupting the integrity of cels
2nd phase - delayed, secondary injury
days to months after trauma, stretching of membrane, unregulated flux of ions, increased glutamate release, cytoskeletal degradation, inflammation, mitochronrial dysfunction, increased oxidative stress, edema, ischemia
neuroinflammation based therapies - minocycline
anti-inflammatory properites, crosses BBB. Conflicting effects in animal models
neuroinflammation based therapies - melatonin
neuroprotective properties, lipophilic. Varying results in animals
neuroinflammation based therapies - statins
neuroprotective and anti-inflammatory properties in mouse model. Suppression of glial activity
neuroinflammation based therapies - stem cells
regenerative therapy. Suppression of inflammation
neuroinflammation based therapies - granulocyte colony stimulating factor
FDA approved, recruits endogenous stem cells to injury site for neuroprotection
changes in excitation and inhibition with TBI are associated with
glutamate and GABA
ionic flux modifications - glutamate induces
depolarization
metabolic crisis with TBI
energy failure by trying to restore ionic homeostasis through ATP pumps activity
Excitoxicity with TBI causes creation of
free radicals and mitochondrial impairments leading to cell death
excess glutamaate stimulation activates
NADPH oxidase - generating oxidative stress
mitochondrial calcium accumulation causes
membrane potential compromise generating free radicals
fluid percussion injury
- Intracranial hemorrhage, brain swelling, grey matter damage, skull fracture
- Mixed focal/diffuse injury
- Highly reproducible
- Requires craniotomy
- High mortality rate
controlled cortical impact
- Impact is created using a pneumatic/electromagnetic devise to drive an impactor onto the intact dura
- Creates focal cortical tissue damage, subdural hemtomas, DAI and disrupts the BBB
- High reproducible
- Low mortality rate
- Requires craniotomy
weight drop impact acceleration injury
- Feeney’s model – dropping weight on intact dura, focal cortical injury, requires craniotomy, resembles human focal TBI but has high mortality rate
- Shohami’s method – close injury model, weight dropped on skull resulting in a fracture. Creates BBB dysfunction, behavioral deficits and inflammation. Easy to execute but not highly reproducible
- Marmarou’s model – skull is surgically exposed and a steel disc is glued to skull and brass weight is dropped. Produces DAI and resembles human injury but as poor reproducibility and high mortality rate
- Maryland Model – like that ^^ but with force applied to the anterior portion of the cranium. Prouces DAI but no skull fracture/contusion
Blast injury
- Mimics TBI amond military
- Animal placed into as shock tube where a compression shock wave is generated
- Creates brain edema, DAI and vasospasm
behavioral changes with TBI
headaches, attention deficits, cognition impairments, sensory processing deficiency, communication deficits, severe depression, anxiety, sleep disturbances, personality changes, aggression,
neuropathology - contusions
areas of cerebral bruising particularly involving gray matter, whereby blood leaks into the extravascular space and it results in cell death and local loss of tissue
neuropathology - diffuse axonal injury
affects white matter throughout the cerebrum and brain stem. Followed by generalized atrophy with ventricular enlargement; takes a few weeks/month to develop
• Usually responsible for slurred speech
assessment of TBI - glasgow coma scale
used soon after injury
• Most common scoring system
• Used to gauge severity of acute injury
• Limitations: drug use, shock or low blood oxygen can lead to inaccurate score
chronic traumatic encephalopathy
o Neurodegenerative syndrome that has been linked to serious psychiatric symptoms including depression and suicidal behavior
o Found in individual with a history of repeated TBI
clinical trials - hypothermia
mild to moderate, decreased mortality and improve rates of neurologic recovery
clinical trials - progesterone
no differential effects
clinical trials - bone marrow
mononuclear cells used in children and adults with severe TBI
clinical trials - deep brain stimulation
central thalamus stimulation for severe TBI, no results yet
