Toll?Like receptor 4 promotes the phosphorylation of CRMP2 via the activation of
Rho?kinase in MCAO rats
#MMPMID29749502
Li XB
; Ding MX
; Ding CL
; Li LL
; Feng J
; Yu XJ
Mol Med Rep
2018[Jul]; 18
(1
): 342-348
PMID29749502
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The mechanism associated with Toll?like receptor 4 (TLR4) in neurological injury
remains unclear. The aim of the present study was to investigate the pathology of
TLR4 in middle cerebral artery occlusion (MCAO)/reperfusion rat models via the
regulation of collapsin response mediator protein 2 (CRMP2) phosphorylation. The
modified neurological severity score (mNSS) was applied to assess neurological
recovery. Immunofluorescence and western blotting were used to detect the protein
expressions of TLR4, Rho?associated protein kinase 2 (ROCK?II) and CRMP2
following the intracerebroventricular administration of TLR4?specific agonist,
lipopolysaccharide (LPS) and TLR4?neutralizing antibody, the ROCK?II specific
inhibitor Y?27632 or LPS+Y?27632 30 min prior to MCAO. The expression levels of
TLR4 and the phosphorylation of CRMP2 significantly increased in response to
LPS?mediated induction and/or MCAO; however, they were reversed by treatment with
LPS+TLR4?neutralizing antibody. Y?27632 decreased the expression of ROCK?II and
phosphorylated (p)?CRMP2, and suppressed the increased ROCK?II and p?CRMP2
induced by LPS; however, no effect on the levels of TLR4 expression was observed.
The neurological function as measured by mNSS score was reduced in the LPS group
when compared with the MCAO group, whereas the LPS+Y?27632 group reversed the
reduced neurological function at 7 and 14 days post?MCAO. The results of the
present study suggested that TLR4 may promote the phosphorylation of CRMP2 via
the activation of ROCK?II in MCAO rats, which further characterizes the
pathological mechanism of TLR4 in stroke, and that modulation of TLR4 could be a
potential target to limit secondary post?stroke brain damage.
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