Objective To explore the protective effect and potential mechanism of pyrroloquinoline quinone (PQQ) on mice with traumatic brain injury (TBI).Methods Sixty C57BL/6 mice were randomly divided into sham operation group,TBI group and PQQ group,with 20 mice in each group.The TBI model was established by controlled cortical impact.The mice in the PQQ group were intraperitoneally injected with PQQ (10 mg/kg) 30 minutes before injury,while the mice in the sham operation and the TBI groups were intraperitoneally injected with the same amount of normal saline.At 24 hours after injury,the neurological function of mice was evaluated by neurological function score,the brain water content was detected by the dry-wet weight method,neuronal apoptosis was detected by TUNEL staining,the levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in brain tissue were detected by ELISA,and the protein expression levels of caspase 3,Notch receptor intracellular domain (NICD),hairy and enhancer of split 1 (HES-1),and ionized calcium-binding adapter molecule 1 (IBA1) of microglia in brain tissue were detected by Western blotting.Results Compared with the sham operation group,the brain water content and neurological function score of the TBI group were significantly increased (P<0.05),the contents of IL-1βand TNF-αin brain tissue were significantly increased (P<0.05),the rate of TUNEL positive cells in brain tissue was significantly increased (P<0.05),and the expression levels of NICD,HES-1,IBA-1 and activated caspase3 in brain tissue were significantly increased (P<0.05).Compared with the TBI group,the brain water content and neurological function score of the PQQ group were significantly decreased (P<0.05),the levels of IL-1βand TNF-αin brain tissue were significantly decreased (P<0.05),the rate of TUNEL positive cells in brain tissue was significantly decreased (P<0.05),the expression levels of NICD and HES-1 in brain tissue were significantly increased,but the expression levels of IBA-1 and activated caspase3 in brain tissue were significantly decreased (P<0.05).Conclusion PQQ can alleviate brain edema,inflammatory response and neuronal apoptosis in TBI mice,improve neurological function,and thus exert a neuroprotective effect.Its mechanism may be related to the activation of the Notch signaling pathway.