Neuroprotective effects of ergothioneine in a mouse model of traumatic brain injury

HUANG Qiuhu; WANG Yao; ZHANG Haowen; ZHONG Wangwang; ZHOU Jian

doi:10.3969/j.issn.1671-2897.2025.05.003

Abstract：Objective To investigate the neuroprotective effect of ergothioneine(EGT)in a mouse model of traumatic brain injury(TBI).Methods A total of 108 adult male ICR mice were randomly divided into the following groups:Sham,TBI,TBI+vehicle and TBI+EGT according to random number table method.TBI models were established by Feeney's method.Mice received 70 mg/kg/day EGT or an equal volume of vehicle for 7 days before TBI.Mice were sacrificed at 24 h after TBI,and the cortex adjacent to the contusion on the same side was extracted.Brain water content was determined by wet-dry weight method;Neurological function was determined by NSS scores;Neuronal survival in the cortical area was evaluated with Nissl staining,and apoptosis was identified by TUNEL staining.Western blotting was used to determine the expression of Cytochrome C,Bax,and Cleaved caspase 3.The detection of Cleaved caspase 3 was performed using immunofluorescence;meanwhile,the levels of Malondialdehyde(MDA)and the enzymatic activity of superoxide dismutase(SOD)were quantified through ELISA assays.Results Compared to the sham group,the brain water content,apoptotic index,and MDA levels in mice following TBI significantly increased,accompanied by a marked decrease in SOD activity and neuronal survival rates(P<0.01).Furthermore,TBI led to a notable reduction in the expression of mitochondrial Cytochrome C,along with an increase in Bax expression(P<0.01)and elevated levels of Cleaved caspase 3.Treatment with ergothioneine resulted in a substantial improvement,as evidenced by a significant decline in brain water content,apoptotic index,and MDA levels,coupled with a notable increase in SOD activity and neuronal survival(P<0.01).Additionally,EGT treatment promoted the upregulation of mitochondrial Cytochrome C expression,downregulation of Bax expression(P<0.05),and a significant reduction in the expression of Cleaved caspase 3.Conclusion EGT can exhibit neuroprotective effects by suppressing the mitochondrial apoptosis and antioxidant stress.