51. Agonistic analog of growth hormone–releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke
- Author
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Ruiping Cai, Fu Ren, Haotian Zhang, Yang Yao, Andrew V. Schally, Yueyang Liu, Jianhua Huang, Qian Xu, Xiaomin Su, Jingyu Yang, Ming-Sheng Zhou, Renzhi Cai, Xiaohang Che, Jialing Cai, Xiaoxiao Fu, and Xianyang Zhang
- Subjects
Male ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Neurogenesis ,Apoptosis ,Tropomyosin receptor kinase B ,Growth Hormone-Releasing Hormone ,CREB ,Neuroprotection ,Mice ,Neural Stem Cells ,Internal medicine ,medicine ,Animals ,Cyclic AMP Response Element-Binding Protein ,Protein kinase B ,Cell Proliferation ,Ischemic Stroke ,Membrane Glycoproteins ,Neuronal Plasticity ,Multidisciplinary ,biology ,business.industry ,Brain-Derived Neurotrophic Factor ,Infarction, Middle Cerebral Artery ,Recovery of Function ,Protein-Tyrosine Kinases ,Biological Sciences ,Growth hormone–releasing hormone ,Neural stem cell ,Nerve Regeneration ,Mice, Inbred C57BL ,Neuroprotective Agents ,Endocrinology ,biology.protein ,business - Abstract
Ischemic stroke can induce neurogenesis. However, most stroke-generated 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.
- Published
- 2021