Edaravone alleviated propofol-induced neural injury in developing rats by BDNF/TrkB pathway.

Abstract

As a variety of free radical scavenger, edaravone has shown its potential in producing antioxidant, anti‐inflammatory and neuroprotective effects in various disease models. However, the underlying mechanism behind the neuroprotective effects of edaravone remained unclear. This study is aimed at determining the effects of edaravone on neuroprotection and anti‐inflammatory through a propofol‐induced neural injury rat model. Firstly, an observation was made of apoptosis and neuroinflammation in the hippocampus of developing under the influence of propofol. It was found out that propofol could produce inflammatory effects in the hippocampus by enhancing the astrogliosis (GFAP) activation and elevating the level of neuronal nitric oxide synthase (nNOS), pro‐inflammatory cytokines interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α). Meanwhile, the increase of apoptosis cells and the decrease of neurons (NeuN) were speculated to aggravate neural injury. Furthermore, it was demonstrated that edaravone intervention can reverse the neural apoptosis and inflammation. Additionally, the intraperitoneal injection of edaravone, the intraperitoneal injection of the brain‐derived neurotrophic factor (BDNF)‐mimicking small compound (7,8 dihydroxyflavone) and the intracranial injection of the exogenous BDNF were all respectively effective in alleviating the propofol‐induced neural apoptosis and inflammation in the hippocampus. It was also found out that edaravone‐activated downstream signalling through tyrosine kinase receptor B (TrkB) receptors in astrocyte, microglia and neuron. However, the neural injury of propofol had no impact on long‐term learning and memory, except causing a short‐term neurotoxicity. In conclusion, edaravone could alleviate the propofol‐induced neural injury in developing rats through BDNF/TrkB pathway.