Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury
Mushftquddin Khan
Hamza Khan
Inderjit Singh
Avtar K.Singh
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.
机标关键词：traumatic brain injurynitric oxidebrain trauma
资助基金：grants from VA merit awards (BX3401 and RX2090)
论文发表日期：2017-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：6( 696-701 )
英文信息