Effects of CC-chemokine receptor 5 on ROCK2 and P-MLC2 expression after focal cerebral ischaemia–reperfusion injury in rats

Abstract

Objective: CC-chemokine receptor 5 (CCR5) plays a pivotal role in reperfusion after stroke. This study assessed and confirmed the effects of CCR5 in experimental stroke via regulation of ROCK/P-MLC pathway.Methods: Male Sprague Dawley (SD) rats were randomly divided into sham group, ischaemia–reperfusion group (I/R group) and DAPTA group (I/R + CCR5 antagonist group). The rats of the I/R group were subjected to transient middle cerebral artery occlusion (tMCAO) for 2 hours, followed by 24 hours of reperfusion. Animals were measured for neurologic deficit, cerebral infarct volume, TUNEL and hematoxylin-eosin (HE) staining. The protein expressions of ROCK2 and P-MLC2(Ser19) were determined by western blot.Results: Pre-treatment with DAPTA displayed significantly improved neurological functional outcome and reduced cerebral lesion compared with the I/R group animals (p < 0.05); HE staining showed that the I/R group had severe neuronal damage in the ischaemia core and penumbral; Compared with the I/R group, ROCK2 and P-MLC2(Ser19) protein expression in the DAPTA group was reduced (p < 0.05).Conclusions: The data demonstrate that CCR5 is correlated with up-regulation of the expression of ROCK2 and P-MLC2(Ser19) in the ischaemia cortex. Treated with CCR5 antagonist protects the brain against focal cerebral ischaemia–reperfusion injury in rats.