Salvianolic Acids for Injection (SAFI) promotes functional recovery and neurogenesis via sonic hedgehog pathway after stroke in mice
| Autor: | Pan Li, Jingru Zhao, Zuyuan Shen, Tingting He, Xiufen Zheng, Yaoru Li, Rong Chen, Cong Zhang, Ye Zhang, Xingyuan Zhu, Xiangjian Zhang, Lili Cui, Lipeng Dong, Ya Wen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Cyclopamine Neurogenesis Subventricular zone Alkenes Mice Random Allocation 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Hedgehog Proteins Sonic hedgehog Brain-derived neurotrophic factor biology business.industry Veratrum Alkaloids Polyphenols Recovery of Function Cell Biology Neural stem cell Hedgehog signaling pathway Mice Inbred C57BL Stroke 030104 developmental biology medicine.anatomical_structure Endocrinology Nerve growth factor chemistry biology.protein business Neuroscience Injections Intraperitoneal 030217 neurology & neurosurgery Drugs Chinese Herbal Signal Transduction |
| Zdroj: | Neurochemistry International. 110:38-48 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2017.09.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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