Remote limb ischemic postconditioning promotes motor function recovery in a rat model of ischemic stroke via the up‐regulation of endogenous tissue kallikrein
| Autor: | Dan Liang, Ce Li, Zheng Wang, Junfa Wu, Bei-Yao Gao, Yulong Bai, Xi-Biao He |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty medicine.drug_class Ischemia Endogeny Bradykinin Neuroprotection Rats Sprague-Dawley 03 medical and health sciences symbols.namesake 0302 clinical medicine Physiology (medical) Internal medicine Lectins Occlusion medicine Animals Pharmacology (medical) Ischemic Postconditioning Postural Balance Pharmacology Cardioprotection Movement Disorders business.industry Anti-Inflammatory Agents Non-Steroidal Infarction Middle Cerebral Artery Original Articles Recovery of Function Receptor antagonist medicine.disease Magnetic Resonance Imaging Rats Up-Regulation Psychiatry and Mental health Disease Models Animal 030104 developmental biology Cardiology Nissl body symbols business Microtubule-Associated Proteins Tissue Kallikreins 030217 neurology & neurosurgery Immunostaining |
| Popis: | 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 (RIPostC) 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 RIPostC treatment for maximum 21 days. The motor function after RIPostC 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 MAP2 immunostaining. Lectin immunostaining was performed to evaluate the microvessel density and area. Results Daily RIPostC 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 RIPostC 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 RIPostC-induced improvements, indicating the specificity of endogenous TK mediating the neuroprotection 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. |
| Databáze: | OpenAIRE |
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