PMID- 28887094 OWN - NLM STAT- MEDLINE DCOM- 20180606 LR - 20180606 IS - 1872-9754 (Electronic) IS - 0197-0186 (Linking) VI - 110 DP - 2017 Nov TI - Salvianolic Acids for Injection (SAFI) promotes functional recovery and neurogenesis via sonic hedgehog pathway after stroke in mice. PG - 38-48 LID - S0197-0186(17)30369-8 [pii] LID - 10.1016/j.neuint.2017.09.001 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Zhang, Ye AU - Zhang Y AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Zhang, Xiangjian AU - Zhang X AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@aliyun.com. FAU - Cui, Lili AU - Cui L AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Chen, Rong AU - Chen R AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Zhang, Cong AU - Zhang C AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Li, Yaoru AU - Li Y AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - He, Tingting AU - He T AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Zhu, Xingyuan AU - Zhu X AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Shen, Zuyuan AU - Shen Z AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Dong, Lipeng AU - Dong L AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Zhao, Jingru AU - Zhao J AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Wen, Ya AU - Wen Y AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Zheng, Xiufen AU - Zheng X AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. FAU - Li, Pan AU - Li P AD - Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. LA - eng PT - Journal Article DEP - 20170905 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Alkenes) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Hedgehog Proteins) RN - 0 (Polyphenols) RN - 0 (Shh protein, mouse) RN - 0 (Veratrum Alkaloids) RN - 0 (salvianolic acid) RN - ZH658AJ192 (cyclopamine) SB - IM MH - Alkenes/*administration & dosage MH - Animals MH - Drugs, Chinese Herbal/*administration & dosage MH - Hedgehog Proteins/*antagonists & inhibitors/metabolism MH - Injections, Intraperitoneal MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neurogenesis/*drug effects/physiology MH - Polyphenols/*administration & dosage MH - Random Allocation MH - Recovery of Function/*drug effects/physiology MH - Signal Transduction/drug effects/physiology MH - Stroke/*drug therapy/metabolism MH - Veratrum Alkaloids/administration & dosage OTO - NOTNLM OT - Neural progenitor cells OT - Neurogenesis OT - Salvianolic Acids for Injection OT - Sonic hedgehog signaling pathway OT - Stroke EDAT- 2017/09/10 06:00 MHDA- 2018/06/07 06:00 CRDT- 2017/09/10 06:00 PHST- 2017/06/28 00:00 [received] PHST- 2017/08/12 00:00 [revised] PHST- 2017/09/01 00:00 [accepted] PHST- 2017/09/10 06:00 [pubmed] PHST- 2018/06/07 06:00 [medline] PHST- 2017/09/10 06:00 [entrez] AID - S0197-0186(17)30369-8 [pii] AID - 10.1016/j.neuint.2017.09.001 [doi] PST - ppublish SO - Neurochem Int. 2017 Nov;110:38-48. doi: 10.1016/j.neuint.2017.09.001. Epub 2017 Sep 5.