Curcumin relieves gas explosion-induced brain injury via TLR4-mediated M2 polarization of microglia

Acute microglia-mediated neuroinflammation and oxidative stress play important roles in the pathogenesis of gas explosion (GE)-induced traumatic brain injury (TBI). Curcumin has documented neuroinflammatory protective properties; however, its effects on gas explosion (GE)-induced TBI and the underlying mechanism remain unclear.

In this study, we established a male rat model of acute TBI and an in vitro model of acute microglial impact injury using shockwave physiotherapy. The effects of curcumin on the extent of the brain injury, as well as the levels of inflammatory cytokines, oxidative stress indicators, microglia polarization, and toll-like receptor 4 (TLR4) protein expression in model rats and microglial cells were evaluated using histological staining, western blotting, qPCR, immunohistochemistry, immunofluorescence, and biochemical assays.

The results showed that curcumin reduced the pathological changes induced by GE and significantly inhibited the expression of neuron-specific enolase (NSE) (P < 0.05), a marker of microglial activation. Curcumin treatment also promoted M2 polarization of microglia (P < 0.05) and reduced the protein expression levels of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB (P < 0.05), and the pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and NLRP3 (P < 0.05). Moreover, curcumin treatment significantly reduced the levels of oxidative stress factors in rat tissues (P < 0.05).

In summary, our findings indicated that curcumin alleviated acute neuroinflammation and oxidative stress induced by GE in vivo and in vitro by inhibiting TLR4-mediated M2 polarization of microglia, thus providing a new treatment target for the neuroinflammation associated with TBI caused by explosives.