Acute-phase hyperbaric oxygen therapy induces differential regulation of NF-κB/COX-2 and NLRP3 inflammasome pathways in traumatic brain injury.

Abstract

The initial injury from TBI damages brain tissue, disrupting blood flow and causing the brain to experience hypoxia. Hypoxia contributes significantly to the persistence of neuroinflammation and the progression of secondary brain injury, ultimately leading to long-term neurological deficits. Hyperbaric oxygen (HBO) therapy is a potential intervention to mitigate hypoxia. In our earlier work, we demonstrated that HBO treatment effectively reduced brain hypoxia in rat models, as indicated by decreased levels of hypoxia-inducible factor (HIF)-1α. Building on these findings, this study aims to investigate the impact of HBO therapy on neuroinflammatory responses following TBI. A total of 44 rats were randomly assigned to 11 groups: one control group, one TBI group, three normobaric groups, three 2 ATA HBO treatment groups, and three 3 ATA HBO treatment groups. Following TBI induction, the treatment groups received six sessions of 1-hour HBO exposure, administered every 12 h. Brain tissue was harvested on days 3, 7, and 14 post-TBI for analysis. Neuroinflammation was evaluated by measuring NF-κB, NLRP3 and caspase-1 expressions, as well as COX-2 activity. The percentage of intact neurons was assessed by hematoxylin-eosin (HE) staining. On days 3, 7, and 14, both the 2 ATA and 3 ATA HBO groups exhibited a trend toward reduced NF-κB protein levels and COX-2 activity compared to the normobaric groups. In contrast, elevated mRNA and protein levels of NLRP3 and caspase-1 were observed in both HBO-treated groups. Moreover, the 2 ATA and 3 ATA HBO groups showed significantly higher percentages of intact neurons than the normobaric groups at all three time points, suggesting a neuroprotective effect. These findings suggest that acute-phase HBO treatment after TBI is associated with suppression of the NF-κB/COX-2 inflammatory pathway while simultaneously enhancing NLRP3 inflammasome expression. This differential regulation may contribute to the observed neuroprotective effect.