Salvianolic Acids for Injection (SAFI) promotes functional recovery and neurogenesis via sonic hedgehog pathway after stroke in mice. (November 2017)

• Record Type: Journal Article
• Authors: Zhang, Ye; Zhang, Xiangjian; Cui, Lili; Chen, Rong; Zhang, Cong; Li, Yaoru; He, Tingting; Zhu, Xingyuan; Shen, Zuyuan; Dong, Lipeng; Zhao, Jingru; Wen, Ya; Zheng, Xiufen; Li, Pan
• Is Part Of: Neurochemistry international. Volume 110(2017)
• Page Start: 38
• Page End: 48
• Publication Date: 2017-11
• Subjects: Stroke -- Salvianolic Acids for Injection -- Neurogenesis -- Neural progenitor cells -- Sonic hedgehog signaling pathway; tPA tissue plasminogen activator -- NPCs neural progenitor cells -- SVZ subventricular zone -- Shh sonic hedgehog -- Smo Smoothened -- BDNF brain derived neurotrophic factor -- NGF nerve growth factor -- SAFI Salvianolic Acids for Injection -- dMCAO distal middle cerebral artery occlusion -- CYC cyclopamine -- HBC 2-hydropropyl-β-cyclodextrin -- BrdU thymidine analog 5-bromo-2-deoxyuridine -- mNSS modified neurological severity score -- DCX doublecortin -- GFAP glial fibrillary acidic protein -- MAP-2 microtubule-associated protein 2 -- Tuj-1 β-tubulin III -- CNPase cyclic nucleotide phosphodiesterase -- vSVZ ventral subventricular zone -- dSVZ dorsal subventricular zone -- OPCs oligodendrocyte progenitor cells -- pMCAO proximal middle cerebral artery occlusion; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2017.09.001
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: There is a pressing need of developing approaches for delayed post-stroke therapy for patients who fail to receive thrombolysis within the narrow time window. Neuroprotection of Salvianolic Acids for Injection (SAFI) for cerebral ischemia-reperfusion injury in acute phase has been well documented. The current study was to determine the influence of SAFI at the subacute phase after stroke in mice, and to elucidate the underlying mechanisms. Adult male C57BL/6 mice were subjected to permanent occlusion of the distal middle cerebral artery (dMCAO), followed by daily intraperitoneal injection of SAFI 24 h after stroke for 14 days. Motor behavior was measured by neurological function evaluations weekly, and proliferation, migration, survival and differentiation of neural progenitor cells (NPCs) were examined with immunohistochemistry. Sonic hedgehog (Shh) inhibitor cyclopamine (CYC) was injected to determine the involvement of Shh pathway in the therapeutic effects of SAFI. The results showed that SAFI led to dramatic brain functional improvement, elevated NPCs proliferation, and prompted long-term survival of newborn neurons in the subventricular zone (SVZ). Up-regulation of Shh, Ptch and nuclear translocation of Gli1 were observed in the peri-infarct region, accompanied with robust production of Brain derived neurotrophic factor (BDNF) and Nerve growth factor (NGF). Simultaneous administration with CYC strikingly attenuated the beneficial outcomes of SAFI as well as abolished SAFI induced BDNF and NGF production. Collectively, our study demonstrated SAFI significantly promoted long-term functional recovery and neurogenesis, which might be dependent on Shh signaling mediated BDNF and NGF production. Therefore, SAFI might serve as a potential clinically translatable therapy during recovery stage after stroke. Highlights: SAFI promotes functional recovery at the subacute phase after stroke in mice. SAFI induces proliferation and survival of NPCs in SVZ and peri-infarct region. SAFI enhances neurogenesis which might be dependent on Shh signaling pathway. SAFI could serve as a potential clinically translatable therapy on recovery stage.