Mild TBI and Concussion Flashcards
How is the concept of viscoelasticity relevant to DAI?
Stretch axons slowly, they’ll stretch.
Stretch them rapidly, they’ll break.
(Thus airbags making the same change in velocity occur over a slightly longer time help you a lot.)
What can be seen axons of the CNS that have been injured?
Axonal swelling followed by degeneration.
What was the experimental set up used to study dynamic stretch-injury of axons in culture? What is stained to identify axon?
Culture Axonal Injury (CAI). Axons run across deformable mesh-work thing. Staining for Tau identifies axons.
What does CAI show to happen right after axonal stretching?
Undulations.
What’s the molecular reason for why breaking an axon is unfixable?
Microtubules when broken undergo “catastrophe” i.e. rapid depolymerization.
What’s the molecular explanation for why axon swelling occurs?
Transport proteins continue to bring vesicles along the axon, but they can’t progress past the break and thus accumulate. (Imagine a bunch of cars continuing to drive across a broken bridge until there’s a big pile-up)
What causes vericose swelling? (i.e. multiple swellings at different points along the axon)
Failure of multiple microtubules at different sites along the axon cause multiple sites of accumulated vesicles.
What drug could you potentially use to prevent axon damage after stretching? How would that work?
Taxol. By stabilizing microtubules, preventing the catastrophic depolymerization.
What sort of ionic dysregulation happens to axons?
Ca++ influx following massive Na+ influx.
What causes the massive Na+ influx into damaged axons?
Na+ channels (NaCh) lose their inactivation gate, allowing Na+ to just pour in down the electrochemical gradient.
What causes the Ca++ influx into damaged axons?
The massive Na+ influx causes the reversal of the Na+/Ca++ exchanger that usually keeps Ca++ very low inside the cell, leading to massive Ca++ influx.
How does NaCh lose its deactivation gate in axonal injury?
Calpain (a protease) chews up the inactivate gate, but spares the channel.
Brains appear to be more vulnerable to DAI after a prior DAI. What might a molecular mechanism for this be? (Why might this happen?)
Post-traumatic increase in NaCh density, aka. sodium channelopathy, aka NaChO. (NaCh density might be increased to compensate for the dysfunctional channels.)
Why can’t you study inertial brain injury (well) in rats?
They’re too small. Would have to generate unfeasible forces to generate equivalent angular accelerations. Or something. Physics and math say so.
Animals of choice for studying rotational acceleration brain injury?
Pigs.
Why do we lose consciousness following brain trauma?
DAI. (but not losing consciousness doesn’t mean there wasn’t damage).
Do in vivo models confirm that repetitive mTBI is worse, and that NaChO is induced by mTBI?
Yup.
With basic imaging, how do you diagnose mTBI?
“By exclusion.” (Not seeing focal lesions…. maybe…?)
Two ways to detect mTBI with advanced neuroimaging?
Diffusion Tensor Imaging (DTI)
Susceptibility Weighted Imaging (SWI)
Is there a serum biomarker for the detection of mTBI in humans?
Not yet, but people are looking at pNFH.
What’s the biggest non-genetic risk factor for AD-like dementia?
TBI
What do AD and Chronic Traumatic Encephalopathy (CTE) have in common, pathologically? (2 things)
amyloid-beta plaques and neurofibrillary tangles
What is thought to cause CTE?
Single severe TBI
Repetitive mTBI
How might beta-amyloid plaques form in CTE?
DAI from TBI releases APP (amyloid precursor protein) from axons.
Can you get NFTs (neurofibrillary tangles) after a single TBI?
Yep.
What’s one notable way that glia react to TBI?
Microglia get angry, become ameboid, and release inflammatory cytokines. (which might be related to atrophy)
