Laisi Li1, Dongyi Zhi1, Yanling Shen2, Kaixiang Liu1, Hao Li1, Jian Chen3. 1. a Department of Neurology , Affiliated Hospital of Guilin Medical University. 2. b Department of Pathology. 3. c Department of Pathophysiology , Guilin Medical University , Guilin , PR China.
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.
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.
Authors: Sheikh F Ahmad; Mushtaq A Ansari; Ahmed Nadeem; Saleh A Bakheet; Raish Mohammad; Sabry M Attia Journal: Mol Neurobiol Date: 2017-04-18 Impact factor: 5.590