Down-regulation of Rho-kinases induce tolerance in Ischemic preconditioning model after transient cerebral ischemia/reperfusion in rats

Background: Ischemic preconditioning (IPC) is a brief episode of ischemia/reperfusion (I/R) that protects the brain from the damage induced by subsequent prolonged ischemia. Aim: To study the neuroprotective mechanism of IPC. Methods: 30 adult male Wistar rats (150 250 g) were divided into three groups 10 rats in each; the first group was sham-operated and served as a control, I/R group of rats subjected to 30 minutes of left common carotid artery occlusion (CCAO) followed by 24-hour of reperfusion, IPC group were treated with three episodes of 5minutes of CCAO with 10 minutes of reperfusion in between, followed by 30 minutes of CCAO and then allowed for reperfusion for 24 hours. Neurobehavioral assessments were evaluated; Rhokinases (ROCK) and nitrite were measured in affected cerebral hemisphere. Results: Rats’ neurological deficits were significantly decreased in the I/R compared with the control group (P < 0.001) whereas rats treated by precondition stimuli showed significant improvement in neurological deficit compared to I/R group (P < 0.001). Nitrite level was significantly increased in the IPC rats compared to both control and I/R groups (P < 0.001). In contrast, the ROCK level was significantly higher in I/R group compared to control group and its level significantly decreased in IPC rats when compared to I/R group (P < 0.001). ROCK correlates negatively with the nitrite (CC = −0.695, P = 0.000). Conclusions: Downregulation of ROCK level following preconditioning stimuli with the potential involvement of Nitric oxide (NO) appear to be one of the neuroprotective mechanisms of IPC protection against a subsequent I/R challenge evidence by improvement in the neurological deficits.