The circadian clock regulator Bmal1 affects traumatic brain injury in rats through the p38 MAPK signalling pathway.

Abstract Traumatic brain injury (TBI) is still one of the main causes of death and disability worldwide. Bmal1 (brain and muscle Arnt-like protein-1) is the most central factor of the circadian rhythms that control life and cells. Studies have shown that Bmal1 is involved in inflammation, oxidative stress, vasodilation, glucose and lipid metabolism. This study explored the effect of Bmal1 on secondary brain injury after TBI in rats and the possible mechanism. We established a rat model of TBI induced by the free fall of a weight in rats. The Western blotting and immunofluorescence results showed that the Bmal1 levels decreased in the cerebral cortex after TBI, especially at 48 h. The effects of Bmal1 levels on rats after TBI were evaluated by brain oedema measurement, adhesive removal tests, behavioural tests, and TUNEL and FJC staining. We found that the recombinant Bmal1 protein increased Bmal1 levels after TBI and reduced brain oedema, neurobehavioural injury, somatosensory disturbances, and nerve cell necrosis and apoptosis. The ELISA results showed that Bmal1 overexpression could reduce the inflammatory factors IL-4 and TNF-α after TBI. In contrast, inhibiting Bmal1 expression had the opposite effect. The changes in Bmal1 levels were closely related to the phosphorylation of p38 MAPK after TBI. In conclusion, a decrease in Bmal1 after TBI may exacerbate pathological symptoms in vivo by activating p38 MAPK phosphorylation.