2. Academic Validation
  3. Agonistic analog of growth hormone-releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke

Agonistic analog of growth hormone-releasing hormone promotes neurofunctional recovery and neural regeneration in ischemic stroke

  • Proc Natl Acad Sci U S A. 2021 Nov 23;118(47):e2109600118. doi: 10.1073/pnas.2109600118.
Yueyang Liu 1 2,  Jingyu Yang 2,  Xiaohang Che 2,  Jianhua Huang 3,  Xianyang Zhang 4 5,  Xiaoxiao Fu 2,  Jialing Cai 2,  Yang Yao 1,  Haotian Zhang 2,  Ruiping Cai 1,  Xiaomin Su 1,  Qian Xu 1,  Fu Ren 6,  Renzhi Cai 4 7,  Andrew V Schally 8 7 9 10 11 12,  Ming-Sheng Zhou 13
Affiliations

Affiliations

  • 1 Department of Physiology, Shenyang Medical College, Shenyang 110034, China.
  • 2 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 3 The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121000, China.
  • 4 Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, Miami, FL 33125.
  • 5 Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136.
  • 6 Department of Anatomy, Shenyang Medical College, Shenyang 110034, China.
  • 7 South Florida VA Foundation for Research and Education, Veterans Affairs Medical Center, Miami, FL 33125.
  • 8 Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, Miami, FL 33125; Andrew.Schally@va.gov zhoums1963@163.com.
  • 9 Division of Medical Oncology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136.
  • 10 Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136.
  • 11 Department of Pathology & Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136.
  • 12 Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136.
  • 13 Department of Physiology, Shenyang Medical College, Shenyang 110034, China; Andrew.Schally@va.gov zhoums1963@163.com.
PMID: 34782465 DOI: 10.1073/pnas.2109600118
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.

Keywords

GHRH agonists; ischemic stroke; neural stem cells; neurogenesis; neuroplasticity.

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