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Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury

摘要:

Mild traumatic brain injury (TBI), also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is asso-ciated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration.The deficiency of nitric oxide (NO), the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mech-anisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha (HIF-1α), a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma.The activity of HIF-1αis regulated by NO via the mech-anism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione (GSNO) and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1αand to induce HIF-1α-de-pendent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.

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作者单位: Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA [1] College of Medicine, University of South Carolina, Columbia, SC, USA [2] Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA;Ralph H. Johnson VA Medical Center, Charleston, SC, USA [3]
期刊: 《中国神经再生研究(英文版)》2017年12卷5期 696-701页 SCIMEDLINEISTICCSCDBP
栏目名称: INVITED REVIEWS
DOI: 10.4103/1673-5374.206632
发布时间: 2017-06-13
基金项目:
grants from VA merit awards
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