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Inhibition of SRC family kinases protects hippocampal neurons and improves
cognitive function after traumatic brain injury
#MMPMID24428562
Liu DZ
; Sharp FR
; Van KC
; Ander BP
; Ghiasvand R
; Zhan X
; Stamova B
; Jickling GC
; Lyeth BG
J Neurotrauma
2014[Jul]; 31
(14
): 1268-76
PMID24428562
show ga
Traumatic brain injury (TBI) is often associated with intracerebral and
intraventricular hemorrhage. Thrombin is a neurotoxin generated at bleeding sites
fater TBI and can lead to cell death and subsequent cognitive dysfunction via
activation of Src family kinases (SFKs). We hypothesize that inhibiting SFKs can
protect hippocampal neurons and improve cognitive memory function after TBI. To
test these hypotheses, we show that moderate lateral fluid percussion (LFP) TBI
in adult rats produces bleeding into the cerebrospinal fluid (CSF) in both
lateral ventricles, which elevates oxyhemoglobin and thrombin levels in the CSF,
activates the SFK family member Fyn, and increases Rho-kinase 1(ROCK1)
expression. Systemic administration of the SFK inhibitor, PP2, immediately after
moderate TBI blocks ROCK1 expression, protects hippocampal CA2/3 neurons, and
improves spatial memory function. These data suggest the possibility that
inhibiting SFKs after TBI might improve clinical outcomes.
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