Edaravone attenuates neuronal apoptosis in hippocampus of rat traumatic brain injury model via activation of BDNF/TrkB signaling pathway

INTRODUCTION: The purpose of our study was to explore the effects of edaravone on rats with traumatic brain injury (TBI) and investigate the underlying mechanism. MATERIAL AND METHODS: All rats were separated randomly into 3 groups as follows: sham group (n = 25), TBI group (n = 25), TBI + edaravone group (n = 25). Edaravone was administered intraperitoneally (i.p.) at a dose of 3 mg/kg at 30 min, 12 h, and 24 h after TBI. The neurological impairment and spatial cognitive function were assessed by the neurologic severity score (NSS) and Morris water maze (MWM), respectively. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to determine the expression levels of caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). Transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay as well as flow cytometry assay was used to determine the apoptosis rate of cells. RESULTS: Edaravone administration significantly attenuated neurological impairment induced by TBI and promoted cognitive function outcome. The expression of BDNF and TrkB was elevated with treatment of edaravone, which was increased after TBI. The expression of apoptosis related proteins such as caspase-3 and Bax-2 was decreased while that of Bcl-2 was enhanced with edaravone administration following TBI. In addition, edaravone treatment reduced TBI-induced cell apoptosis in the hippocampus. CONCLUSIONS: Our study showed that administration with edaravone was able to inhibit neuronal apoptosis in the hippocampus in a rat TBI model. The neuroprotective function of edaravone may relate to modulation of the BDNF/TrkB signaling pathway.