Early Hyperbaric Oxygen Treatment Attenuates Burn-Induced Neuroinflammation by Inhibiting the Galectin-3-Dependent Toll-Like Receptor-4 Pathway in a Rat Model

Abstract: Hyperbaric oxygen (HBO) treatment has been proven to decrease neuroinflammation inrats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effectsof HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague-Dawley(SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burnwith sham HBO treatment; (2) sham burn with HBO treatment; (3) burn with one-week shamHBO treatment; (4) burn with two-week sham HBO treatment; (5) burn with one-week HBOtreatment; and (6) burn with two-week HBO treatment. SD rats that received third-degree burninjury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression ofproteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway throughenzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Westernblotting. A behavior test was also conducted, which revealed that HBO treatment significantlysuppressed mechanical hypersensitivity in the burn with HBO treatment group compared to the burnwith sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor α (TNF-α)and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin significantlydecreased in the burn with HBO treatment group compared with the burn with sham HBO treatmentgroup (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced theexpression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis showed thatthe expression of Gal-3, TLR-4, CD68 and CD45 in the dorsal horn of the spinal cord was significantlylower in the burn with HBO treatment group than in the burn with sham HBO treatment group(p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the righthind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor in theright hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved thatearly HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, andsuppresses microglia and macrophage activation in a rat model.