Remote limb ischemic postconditioning promotes motor function recovery in a rat model of ischemic stroke via the up‐regulation of endogenous tissue kallikrein

摘要

Summary Aims Remote ischemic conditionings, such as pre‐ and per‐conditioning, are known to provide cardioprotection in animal models of ischemia. However, little is known about the neuroprotection effect of postconditioning after cerebral ischemia. In this study, we aim to evaluate the motor function rescuing effect of remote limb ischemic postconditioning ( RIP ostC) in a rat model of acute cerebral stroke. Methods Left middle cerebral artery occlusion ( MCAO ) was performed to generate the rat model of ischemic stroke, followed by daily RIP ostC treatment for maximum 21 days. The motor function after RIP ostC was assessed with foot fault test and balance beam test. Local infarct volume was measured through MRI scanning. Neuronal status was evaluated with Nissl''s, HE , and MAP 2 immunostaining. Lectin immunostaining was performed to evaluate the microvessel density and area. Results Daily RIP ostC for more than 21 days promoted motor function recovery and provided long‐lasting neuroprotection after MCAO . Reduced infarct volume, rescued neuronal loss, and enhanced microvessel density and size in the injured areas were observed. In addition, the RIP ostC effect was associated with the up‐regulation of endogenous tissue kallikrein ( TK ) level in circulating blood and local ischemic brain regions. A TK receptor antagonist HOE ‐140 partially reversed RIP ostC‐induced improvements, indicating the specificity of endogenous TK mediating the neuroprotection effect of RIP ostC. Conclusion Our study demonstrates RIP ostC treatment as an effective rehabilitation therapy to provide motor function recovery and alleviate brain impairment in a rat model of acute cerebral ischemia. We also for the first time provide evidence showing that the up‐regulation of endogenous TK from remote conditioning regions underlies the observed effects of RIP ostC.