The neuroprotection of hyperbaric oxygen therapy against traumatic brain injury via NF-κB/MAPKs-CXCL1 signaling pathways.

It is well known that hyperbaric oxygen (HBO) therapy achieves neuroprotective effects by modulating neuroinflammatory responses. However, its underlying therapeutic mechanisms are not yet fully elucidated. Based on our previous studies, we further investigated whether HBO therapy exerts neuroprotective effects in vivo by regulating the nuclear factor-kappa B (NF-κB)/ mitogen-activated protein kinases (MAPKs) chemokine (C-X-C motif) ligand (CXCL)1 inflammatory pathway. In our study, a rat model of traumatic brain injury (TBI) was established by controlled cortical impact (CCI) to verify that the expression of CXCL1 and chemokine (C-X-C motif) receptor (CXCR)2 increased after TBI, and CXCL1 was mainly expressed in astrocytes, while CXCR2 was mainly expressed in neurons. Increased apoptosis of cortical nerve cells in the injured cortex was also found after TBI. Reduced nerve cell apoptosis with improved neurological function was observed after application of a CXCR2 antagonist. The expression of phospho-extracellular signal-regulated kinase (p-ERK), phospho-c-Jun N-terminal kinase (p-JNK) and p-NF-κB increased after TBI, and application of ERK, JNK and NF-κB inhibitors decreased expression of CXCL1 and CXCR2 in rats. We further found that HBO therapy down-regulated the expression of p-ERK, p-JNK, p-NF-κB, CXCL1, and CXCR2, and reduced nerve cell apoptosis, improved the neurological function of TBI rats, and ultimately alleviated the secondary injury. In conclusion, HBO therapy may exert neuroprotective effect by regulating the NF-κB/MAPKs (JNK and ERK)-CXCL1 inflammatory pathways following TBI, which probably provide the theoretical and experimental basis for the clinical application of HBO therapy in the treatment of TBI.

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

OBJECTIVE: The 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. METHODS: The 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. RESULTS: TBI-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. CONCLUSIONS: This 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.