Hyperbaric oxygen therapy improves neurological function via the p38-MAPK/CCL2 signaling pathway following traumatic brain injury.

Abstract

ObjectiveThe anti-inflammatory mechanisms of hyperbaric oxygenation (HBO) treatment on traumatic brain injury (TBI)-induced neuroinflammation remain unclear. The aim of this study was expected the effect of HBO on CCL2-related signaling pathway following severe TBI in rats.MethodsThe severe TBI model in rats was induced by controlled cortical impact. TBI rats were treated with CCR2 antagonist, p38 inhibitor, or HBO. Modified neurological severity scores and Morris water maze were used to evaluate neurological and cognitive function. The expression levels of CCL2 and CCR2 were measured by ELISA and real-time fluorescence quantitative PCR. Phospho-p38 expression was analyzed by western blotting.ResultsTBI-induced upregulation of CCL2, CCR2, and p38 in the injured cortex. Application of CCR2 antagonist improved neurological and cognitive function of TBI rats. Application of p38 inhibitor decreased expression of CCL2 and CCR2 in the injured of TBI rats, meanwhile improved neurological and cognitive function. HBO improved neurological and cognitive function by decreasing the expressions of CCL2, CCR2, and phospho-p38.ConclusionsThis study indicates that the p38-MAPK–CCL2 signaling pathway could mediate neuroinflammation and HBO therapy can modulate neuroinflammation by modulating the p38-MAPK–CCL2 signaling pathways following TBI. This study may provide theoretical evidence for HBO treatment in the treatment of TBI.