Withaferin A alleviates cerebral edema by inhibiting AQP4 expression in the brain tissue of rats with traumatic brain injury
10.12007/j.issn.0258-4646.2025.10.012
- VernacularTitle:醉茄素A通过抑制创伤性脑损伤大鼠脑组织AQP4表达减轻脑水肿
- Author:
Wenzheng DONG
1
;
Ping CHEN
;
Xuanxin LIU
;
Qi GAO
;
Bing WANG
Author Information
1. 周口市中心医院神经外科,河南周口 466000
- Publication Type:Journal Article
- Keywords:
withaferin A;
traumatic brain injury;
brain edema;
aquaporin 4
- From:
Journal of China Medical University
2025;54(10):931-936
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of withaferin A on aquaporin 4(AQP4)expression and brain edema in rats with traumatic brain injury(TBI).Methods A TBI rat model was established using the modified free-fall Feeney method,following which the rats were divided into model group and low-dose,medium-dose and high-dose withaferin A groups.Another sham operation group was set up,with 15 rats in each group.Withaferin A was administered once a day by intraperitoneal injection for seven consecutive days.The neurological function of the rats was evaluated using the neurological severity score(NSS),the brain water content was measured using the dry-wet spe-cific gravity method,the blood brain barrier permeability was measured using the Evans Blue method,and the histopathological changes of the cerebral cortex were observed by HE staining.Further,the apoptosis level of the hippocampal cells was observed by TUNEL staining and the expression levels of AQP4 mRNA in the cerebral cortex was detected by real-time quantitative PCR.The expression levels of rhe AQP4 protein in the cerebral cortex,and that of Bax,Bcl-2 and cleaved caspase-3 proteins in the hippocampus were detected by Western blotting.Results Medium and high doses of disolanesin A significantly improved the histopathological changes in the cerebral cortex and decreased the neurological impairment,brain water content and blood brain barrier permeability scores in TBI rats.Simultaneously,A QP4 mRNA and protein expression levels in the cerebral cortex,and Bax and cleaved caspase-3 protein expression and apoptosis levels in the hippocampal tissues of TBI rats decreased;however,Bcl-2 protein expression levels increased.Conclusion Withaferin A can reduce brain edema after TBI and improve neurological function.The mechanism may be related to the inhibition of AQP4 expression.