Toll‑Like receptor 4 promotes the phosphorylation of CRMP2 via the activation of Rho‑kinase in MCAO rats.

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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