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We have previously reported that BBB damage was initially damaged in non\u2010infarcted striatum after acute ischaemia stroke. However, the underlying mechanism is not clear. Since acute ischaemic stroke could induce a significant increase of dopamine release in striatum, in current study, our aim is to investigate the role of dopamine receptor signal pathway in BBB integrity injury after acute ischaemia using rat middle cerebral artery occlusion model. Our data showed that 2\u2010h ischaemia induced a significant increase of endogenous tissue plasminogen activator (tPA) in BBB injury area and intra\u2010striatum infusion of tPA inhibitor neuroserpin, significantly alleviated 2\u2010h ischaemia\u2010induced BBB injury. In addition, intra\u2010striatum infusion of D1 receptor antagonist SCH23390 significantly decreased ischaemia\u2010induced upregulation of endogenous tPA, accompanied by decrease of BBB injury and occludin degradation. More important, inhibition of hypoxia\u2010inducible factor\u20101 alpha with inhibitor YC\u20101 significantly decreased 2\u2010h ischaemia\u2010induced endogenous tPA upregulation and BBB injury. Taken together, our data demonstrate that acute ischaemia disrupted BBB through activation of endogenous tPA via HIF\u20101\u03b1 upregulation, thus representing a new therapeutic target for protecting BBB after acute ischaemic stroke.<\/jats:p>","DOI":"10.1111\/jcmm.15570","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T06:09:39Z","timestamp":1594015779000},"page":"9255-9266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["D1 receptor\u2010mediated endogenous tPA upregulation contributes to blood\u2010brain barrier injury after acute ischaemic stroke"],"prefix":"10.1111","volume":"24","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 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