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function recovery in a rat model of ischemic stroke via the

up-regulation of endogenous tissue kallikrein

Dan Liang I xi-biao He?| Zheng Wang I Ce Lil I bei-yao Gaol I jun-fa Wul

yu-long Bail D

Department of Rehabilitation Medicine

Huashan Hospital Fudan University, Shanghai, 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

Sciences, Shanghai, China

Department of Neurology. He

the neuroprotection effect of postconditioning after cerebral ischemia. In this study,

we aim to evaluate the motor function rescuing effect of remote limb ischemic post

China

Methods: Left middle cerebral artery occlusion (MCAO)was performed to generate

yu-long Bai, Department of Rehabilitation

the rat model of ischemic stroke, followed by daily Ripostc treatment for maximum

Medicine, Huashan Hospital, Fudan Universit 21 days. The motor function after Ripostc was assessed with foot fault test and bal

Email:dr_bail@fudan.edu.cn

ance beam test. Local infarct volume was measured through MRI scanning Neuronal

status was evaluated with Nissl,'s, HE, and MAP2 immunostaining Lectin immunostain

National Natural Science Foundation of

ing was performed to evaluate the microvessel density and are

China. Grant/Award Number: 81372119 and Results: Daily Ripostc for more than 21 days promoted motor function recovery and

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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 Ripostc effect was associated with the up-regulation of

endogenous tissue kallikrein (T K)level in circulating blood and local ischemic brain

regions. A TK receptor antagonist hoe-140 partially reversed ripostc-induced im

provements, indicating the specificity of endogenous TK mediating the neuroprotec

tion effect of Ripostc

Conclusion: Our study demonstrates Ripostc 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 Ripostc

KEY WORDS

cerebral ischemia, rehabilitation, remote limb ischemic postconditioning, tissue kallikrein