TBI: Neurodegeneration Flashcards
What is the relation between TBI and cognitive decline?
Both single and repetitive injuries predisposes individuals to late cognitive decline
Who and what kind of evidence was used to show that TBI plays a role in cognitive decline?
Studying patterns of network dysfunction suggests that TBI can trigger neurodegeneration, and that this response is a major determinant of long-term outcome (Smith et al., 2013).
What are the characteristics of TBI neurodegeneration?
Accumulation of varying amounts of amyloid-β plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which are hallmarks of AD.
How does neurodegeneration spread following TBI?
Misfolded proteins can pass from neuron to neuron via prion-like trans-synaptic spread.
What evidence has been used to suggest a model for tau spread?
Studies in rodents have shown that aggregated tau can initiate the formation of neurofibrillary tangles, and that this process can spread trans-synaptically from an initially affected brain region to remote but functionally connected areas.
Do pathogenic proteins just spread anywhere?
The spread of pathogenic proteins is likely to be constrained by the organization of white matter tracts.
Where does atrophy occur after TBI (who showed this?)?
Regionally selective atrophy after TBI is common in parts of the DMN (Warner et al., 2010) in a similar manner to AD
What does computational modelling tell us about neurodegenerative spread after TBI? (and who?)
Computational modelling to simulate the possible spread of abnormal proteins along white matter tracts shows that a simple diffusion mechanism could produce the observed complex patterns of brain atrophy, in the absence of selective vulnerability or regional specificity to neurodegeneration (Raj et al., 2010).
What other factors are thought to contribute to atrophy following TBI?
Chronic microglial activation (CMA) which can persist for months to years after TBI was thought to contribute to atrophy.
What does evidence show about CMA in neurodegeneration following TBI? (and who?)
CMA is neuroprotective in TBI mouse models through accelerated deterioration after administration of microglial activation suppressing Minocycline (Scott et al., 2018).
