D1 receptor-mediated endogenous tPA upregulation contributes to blood-brain barrier injury after acute ischaemic stroke.

D1 receptor-mediated endogenous tPA upregulation contributes to blood-brain barrier injury after acute ischaemic stroke. J Cell Mol Med. 2020 Jul 06;: Authors: Wang Y, Wang X, Zhang X, Chen S, Sun Y, Liu W, Jin X, Zheng G Abstract Blood-brain barrier (BBB) integrity injury within the thrombolytic time window is becoming a critical target to reduce haemorrhage transformation (HT). We have previously reported that BBB damage was initially damaged in non-infarcted 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-h ischaemia induced a significant increase of endogenous tissue plasminogen activator (tPA) in BBB injury area and intra-striatum infusion of tPA inhibitor neuroserpin, significantly alleviated 2-h ischaemia-induced BBB injury. In addition, intra-striatum infusion of D1 receptor antagonist SCH23390 significantly decreased ischaemia-induced upregulation of endogenous tPA, accompanied by decrease of BBB injury and occludin degradation. More important, inhibition of hypoxia-inducible factor-1 alpha with inhibitor YC-1 significantly decreased 2-h ischaemia-induced endogenous tPA upregulation and...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research