1. Agonistic analog of growth hormone-releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke.
- Author
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Yueyang Liu, Jingyu Yang, Xiaohang Che, Jianhua Huang, Xianyang Zhang, Xiaoxiao Fu, Jialing Cai, Yang Yao, Haotian Zhang, Ruiping Cai, Xiaomin Su, Qian Xu, Fu Ren, Renzhi Cai, Schally, Andrew V., and Ming-Sheng Zhou
- Subjects
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ISCHEMIC stroke , *SOMATOTROPIN , *NEURAL stem cells , *ARTERIAL occlusions , *CELL survival , *COMMERCIAL products - Abstract
Ischemic stroke can induce neurogenesis. However, most strokegenerated newborn neurons cannot survive. It has been shown that MR-409, a potent synthetic agonistic analog of growth hormone-releasing hormone (GHRH), can protect against some life-threatening pathological conditions by promoting cell proliferation and survival. The present study shows that long-term treatment with MR-409 (5 or 10 µg/mouse/d) by subcutaneous (s.c.) injection significantly reduces the mortality, ischemic insult, and hippocampal atrophy, and improves neurological functional recovery in mice operated on for transient middle cerebral artery occlusion (tMCAO). Besides, MR-409 can stimulate endogenous neurogenesis and improve the tMCAO-induced loss of neuroplasticity. MR-409 also enhances the proliferation and inhibits apoptosis of neural stem cells treated with oxygen and glucose deprivation-reperfusion. The neuroprotective effects of MR-409 are closely related to the activation of AKT/CREB and BDNF/TrkB pathways. In conclusion, the present study demonstrates that GHRH agonist MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis in cerebral ischemic mice. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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