Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC

• DOI: 10.1016/j.phrs.2022.106641
• Publication Date: 2022-12-29T11:46:11Z
• Authors: Qianyan He; Yinzhong Ma; Cheng Fang; Zijun Deng; Fang Wang; Yang Qu; Meifang Yin; Ruoyu Zhao; Dianhui Zhang; Fuyou Guo; Yi Yang; Junlei Chang; Zhen-Ni Guo
• Keywords: Stroke; Platelet-derived growth factor

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated increased blood-brain barrier (BBB) disruption and hemorrhagic transformation. Remote conditioning (RIC) has demonstrated neuroprotective effects against stroke. However, whether how RIC regulates rtPA-associated BBB remains unclear. Here, a rodent model thromboembolic followed by rtPA thrombolysis at different time points was performed or without RIC. Brain infarction, neurological outcomes, permeability, intracerebral hemorrhage were assessed. The platelet-derived growth factor CC (PDGF-CC)/PDGFRα pathway in brain tissue, PDGF-CC levels skeletal muscle peripheral blood also measured. Furthermore, impact on serum measured healthy subjects AIS patients. Our results showed that substantially reduced injury, hemorrhage, cerebral deficits after stroke, even when administrated delayed therapeutic window. Mechanistically, significantly decreased PDGFRα activation levels, which partially resulted from reduction RIC-applied hindlimbs platelets. Intravenous intraventricular supplementation abolished protective integrity. Moreover, similar changes observed humans Together, our study demonstrates can attenuate rtPA-aggravated via reducing PDGF-CC/PDGFRα thus supports as potential approach for prevention treatment following thrombolysis.