{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:42:49Z","timestamp":1781836969416,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,2,4]],"date-time":"2018-02-04T00:00:00Z","timestamp":1517702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81372119"],"award-info":[{"award-number":["81372119"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501134"],"award-info":[{"award-number":["81501134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Remote ischemic conditionings, such as pre\u2010 and per\u2010conditioning, 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 (<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC) in a rat model of acute cerebral stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Left middle cerebral artery occlusion (<jats:styled-content style=\"fixed-case\">MCAO<\/jats:styled-content>) was performed to generate the rat model of ischemic stroke, followed by daily<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC treatment for maximum 21\u00a0days. The motor function after<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC was assessed with foot fault test and balance beam test. Local infarct volume was measured through<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>scanning. Neuronal status was evaluated with Nissl's,<jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>, and<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>2 immunostaining. Lectin immunostaining was performed to evaluate the microvessel density and area.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Daily<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC for more than 21\u00a0days promoted motor function recovery and provided long\u2010lasting neuroprotection after<jats:styled-content style=\"fixed-case\">MCAO<\/jats:styled-content>. Reduced infarct volume, rescued neuronal loss, and enhanced microvessel density and size in the injured areas were observed. In addition, the<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC effect was associated with the up\u2010regulation of endogenous tissue kallikrein (<jats:styled-content style=\"fixed-case\">TK<\/jats:styled-content>) level in circulating blood and local ischemic brain regions. A<jats:styled-content style=\"fixed-case\">TK<\/jats:styled-content>receptor antagonist<jats:styled-content style=\"fixed-case\">HOE<\/jats:styled-content>\u2010140 partially reversed<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC\u2010induced improvements, indicating the specificity of endogenous<jats:styled-content style=\"fixed-case\">TK<\/jats:styled-content>mediating the neuroprotection effect of<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>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\u2010regulation of endogenous<jats:styled-content style=\"fixed-case\">TK<\/jats:styled-content>from remote conditioning regions underlies the observed effects of<jats:styled-content style=\"fixed-case\">RIP<\/jats:styled-content>ostC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12813","type":"journal-article","created":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T04:46:36Z","timestamp":1517805996000},"page":"519-527","source":"Crossref","is-referenced-by-count":38,"title":["Remote limb ischemic postconditioning promotes motor function recovery in a rat model of ischemic stroke via the up\u2010regulation of endogenous tissue kallikrein"],"prefix":"10.1111","volume":"24","author":[{"given":"Dan","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine Huashan Hospital Fudan University Shanghai 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