HIF-1α participates in secondary brain injury through regulating neuroinflammation

A deeper understanding of the underlying biological mechanisms of secondary brain injury induced by traumatic brain injury (TBI) will greatly advance the development of effective treatments for patients with TBI. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a central regulator of cellular response to hypoxia. In addition, growing evidence shows that HIF-1 alpha plays the important role in TBI-induced changes in biological processes; however, detailed functional mechanisms are not completely known. The aim of the present work was to further explore HIF-1 alpha-mediated events after TBI. To this end, next-generation sequencing, coupled with cellular and molecular analysis, was adopted to interrogate vulnerable events in a rat controlled cortical impact model of TBI. The results demonstrated that TBI induced accumulation of HIF-1 alpha at the peri-injury site at 24 h post-injury, which was associated with neuronal loss. Moreover, gene set enrichment analysis unveiled that neuroinflammation, especially an innate inflammatory response, was significantly evoked by TBI, which could be attenuated by the inhibition of HIF-1 alpha. Furthermore, the inhibition of HIF-1 alpha could mitigate the activation of microglia and astrocytes. Taken together, all these data implied that HIF-1 alpha might contribute to secondary brain injury through regulating neuroinflammation.

Automated summary

A deeper understanding of the underlying biological mechanisms of secondary brain injury induced by TBI, especially the role of HIF-1 alpha in regulating neuroinflammation, could advance the development of effective treatments for TBI patients. This study utilized next-generation sequencing and cellular analysis to investigate HIF-1 alpha-mediated events in a rat TBI model. The results demonstrated that TBI induced the accumulation of HIF-1 alpha and neuroinflammation, and the inhibition of HIF-1 alpha could attenuate these effects, suggesting its contribution to secondary brain injury.