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.

Background: To investigate the neuroprotective effect of edaravone on excessive-dose propofol-induced neurotoxicity in the hippocampus of newborn rats and HT22 cells.Methods: Cell proliferation was investigated by assessing ki67 expression in the neural stem of the hippocampus of newborn rats and by cell counting kit-8 (CCK8) assay in HT22 cells. Cell apoptosis was assessed in vivo by caspase 3 detection in Western blots and measurement of apoptosis in neurons and glial cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Apoptosis was analyzed by flow cytometry in HT22 cells. The Morris water maze was used to evaluate the long-term learning and memory ability of rats. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expression of mBDNF/TrkB/PI3K pathway-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction (q-RT PCR). Results: In neonatal rat hippocampus and HT22 cells, edaravone increased cell proliferation and decreased cell apoptosis after excessive propofol-induced neurotoxicity. In addition, the levels of proinflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF)-α were reduced by edaravone pretreatment. The use of the tropomyosin receptor kinase B (TrkB) antagonist ANA-12 and TrkB agonist 7,8DHF with propofol groups showed that edaravone mitigated excessive propofol-induced neurotoxicity through the mature brain-derived neurotrophic factor (mBDNF)/TrkB/phosphoinositide 3-kinase (PI3K) pathway. However, the current dose of propofol did not significantly affect long-term learning and memory in rats. Conclusion: Edaravone pretreatment ameliorated propofol-induced proliferation inhibition, neuroapoptosis, and neural inflammation by activating the mBDNF/TrkB/PI3K pathway.

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