Abstract

Hyperbaric oxygen (HBO) treatment has been proven to decrease neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of 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 burn with sham HBO treatment; (2) sham burn with HBO treatment; (3) burn with one-week sham HBO treatment; (4) burn with two-week sham HBO treatment; (5) burn with one-week HBO treatment; and (6) burn with two-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting. A behavior test was also conducted, which revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared to the burn with 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 significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression 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 that the expression of Gal-3, TLR-4, CD68 and CD45 in the dorsal horn of the spinal cord was significantly lower 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 right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia and macrophage activation in a rat model.

Highlights

  • Neuroinflammation is connected to the activation of microglia [1]

  • Rats were divided into the following six groups (n = 6 per group): (1) sham burn with sham Hyperbaric oxygen (HBO) treatment; (2) sham burn with HBO treatment: normal rats were sacrificed after 1-week HBO treatment; (3) burn with 1-week sham HBO treatment: experimental animals were sacrificed at 1 week after burn injury; (4) burn with 2-week sham HBO treatment: experimental animals were sacrificed at 2 weeks after burn injury; (5) burn with 1-week HBO treatment: after burn injury, experimental animals were sacrificed 1 week after HBO treatment; and (6) burn with 2-week HBO treatment: after burn injury, experimental animals were sacrificed after 2-week HBO treatment

  • Our data indicated that early HBO treatment inhibits the Gal-3-dependent Toll-like receptor-4 (TLR-4) pathway

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Summary

Introduction

Microglial cells are the primary macrophages of the central nervous system (CNS), and these cells modulate neuroinflammation and neuronal death [2]. Hyperbaric oxygen (HBO) therapy is a low-cost medical treatment with few side effects and uses reusable equipment. HBO has been commonly applied for many diseases; in this therapy, patient breathes 100% oxygen at more than 1.4 atmosphere absolute (ATA) [6]. HBO treatment exerts neuroprotective effects through various mechanisms, including the inhibition of inflammation, reduction of hypoxia, and improvement of microcirculation in the nervous system [7]. HBO therapy is applied for many types of central or peripheral nerve injury diseases. HBO treatment can promote the recovery of injured nerves and the regeneration of peripheral nerves by improving tissue oxygen supplementation. The anti-inflammatory effects of HBO therapy have been demonstrated in an animal model [12,13,14,15,16]

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