Salvianolic acids enhance cerebral angiogenesis and neurological recovery by activating JAK2/STAT3 signaling pathway after ischemic stroke in mice. Issue 1 (14th September 2017)

• Record Type: Journal Article
• Authors: Li, Yaoru; Zhang, Xiangjian; Cui, Lili; Chen, Rong; Zhang, Ye; Zhang, Cong; Zhu, Xingyuan; He, Tingting; Shen, Zuyuan; Dong, Lipeng; Zhao, Jingru; Wen, Ya; Zheng, Xiufen; Li, Pan
• Is Part Of: Journal of neurochemistry. Volume 143:Issue 1(2017)
• Page Start: 87
• Page End: 99
• Publication Date: 2017-09-14
• Subjects: angiogenesis -- ischemic stroke -- JAK2/STAT3 -- neurological recovery -- Salvianolic acids; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14140
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract : Post‐stroke angiogenesis contributes to long‐term neurological recovery. We demonstrated that Salvianolic acids (Sals) significantly enhanced angiogenesis and improved neurological recovery in ischemic brain. These effects may be dependent on the activation of JAK2/STAT3 signaling pathway which further regulated vascular endothelial growth factor, Ang‐1, and Ang‐2 expression. It may represent a therapeutic target and provide an alternative strategy for potential clinical trials. Abstract: Post‐stroke angiogenesis facilitates neurovascular remodeling process and promotes neurological recovery. Proangiogenic effects of Salvianolic acids (Sals) have been reported in various ischemic disorders. However, the underlying mechanisms are still poorly understood. Previous studies of our laboratory have demonstrated that activating Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the protection against cerebral ischemia/reperfusion injury. In this study, we investigated the impacts of Sals on angiogenesis and long‐term neurological recovery after ischemic stroke as well as the potential mechanisms. Male mice subjected to permanent distal middle cerebral artery occlusion were administrated with Sals, 5‐bromo‐2′‐deoxyuridine, and JAK2 inhibitor AG490 once daily from day 1 to day 14 after distal middle cerebral artery occlusion. Compared with the control group, Sals treatment significantly improved neurological recovery at day 14 and 28 after ischemic stroke. Sals enhanced post‐stroke angiogenesis, pericytes and astrocytic endfeet covered ratio in the peri‐infarct area. The JAK2/STAT3 signaling pathway was activated by Sals in the angiogenesis process, and inhibition of JAK2/STAT3 signaling blocked the effects of Sals on post‐stroke angiogenesis and neurological recovery as well as abolished the mediation of proangiogenic factors. In summary, these data suggest that Sals administration enhances cerebral angiogenesis and promotes neurological recovery after ischemic stroke, mediated by the activation of JAK2/STAT3 signaling pathway.