| 摘要: | Traumatic brain injury (TBI) is a major cause of disability and death worldwide. Its pathophysiology involves oxidative stress and inflammation, but effective treatments remain elusive. Recent studies have revealed a critical link between TBI and disrupted circadian rhythms, but the detailed mechanisms were not fully understood. Motivated by the observed decrease in Rev-erbα levels after TBI, we aimed to investigate the role of Rev-erbα in the pathophysiology of TBI and its potential as a therapeutic target.
By conducting a mouse model of TBI, we found that TBI significantly reduces Rev-erbα levels, exacerbating inflammatory and oxidative stress pathways. Pharmacological modulation of Rev-erbα, either by activation or inhibition, bidirectionally influenced the inflammatory and oxidative events, which in turn affected neurobehavioral outcomes, highlighting Rev-erbα's protective role. Mechanistically, Rev-erbα regulates the expression of key genes involved in oxidative stress and inflammation.
The reduction in Rev-erbα following TBI likely contributes to increased oxidative damage and inflammation, creating an unfavorable environment for neuronal survival and recovery. This detrimental effect could be reversed by pharmacological activation of Rev-erbα. The findings suggest that targeting Rev-erbα has therapeutic potential to mitigate TBI-induced damage and improve outcomes, particularly in populations susceptible to TBI with disrupted circadian regulation.
Traumatic brain injury (TBI) is a major cause of disability and death worldwide. Its pathophysiology involves oxidative stress and inflammation, but effective treatments remain elusive. Recent studies have revealed a critical link between TBI and disrupted circadian rhythms, but the detailed mechanisms were not fully understood. Motivated by the observed decrease in Rev-erbα levels after TBI, we aimed to investigate the role of Rev-erbα in the pathophysiology of TBI and its potential as a therapeutic target.
By conducting a mouse model of TBI, we found that TBI significantly reduces Rev-erbα levels, exacerbating inflammatory and oxidative stress pathways. Pharmacological modulation of Rev-erbα, either by activation or inhibition, bidirectionally influenced the inflammatory and oxidative events, which in turn affected neurobehavioral outcomes, highlighting Rev-erbα's protective role. Mechanistically, Rev-erbα regulates the expression of key genes involved in oxidative stress and inflammation.
The reduction in Rev-erbα following TBI likely contributes to increased oxidative damage and inflammation, creating an unfavorable environment for neuronal survival and recovery. This detrimental effect could be reversed by pharmacological activation of Rev-erbα. The findings suggest that targeting Rev-erbα has therapeutic potential to mitigate TBI-induced damage and improve outcomes, particularly in populations susceptible to TBI with disrupted circadian regulation. |
