GLP-1R Agonist Exendin-4 Protects Against Hemorrhagic Transformation Induced by rtPA After Ischemic Stroke via the Wnt/β-Catenin Signaling Pathway

• DOI: 10.1007/s12035-022-02811-9
• Publication Date: 2022-03-31T21:03:59Z
• Authors: Chengli Liu; Shanshan Sun; Jie Xie; Hui Li; Tianyu Li; Qiqi Wu; Yongsheng Zhang; Xiangjun Bai; Jian Wang; Xin Wang; Zhanfei Li; Wei Wang
• Keywords: Ex vivo; Evans Blue

Tissue plasminogen activator (tPA) is recommended by the FDA to dissolve intravascular clots after acute ischemic stroke (AIS). However, it may contribute hemorrhagic transformation (HT). The Wnt/β-catenin signaling pathway plays an important role in regulating blood-brain barrier (BBB) formation central nervous system. We explored whether glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4) reduces risk of HT rtPA treatment via using a rat transient middle cerebral artery occlusion (MCAO) model vivo and oxygen-glucose deprivation plus reoxygenation (OGD/R) vitro. Our results showed that EX-4 attenuated neurological deficits, brain edema, infarct volume, BBB disruption, rtPA-induced stroke. suppressed production ROS activation MMP-9 protect integrity activating pathway. PRI-724, selective inhibitor β-catenin, was able reverse therapeutic effect Therefore, our indicate GLP-1R be potential agent decrease