Neuroprotective effect of ketamine against TNF‐α‐induced necroptosis in hippocampal neurons

Tumour necrosis factor‐α (TNF‐α), a crucial cytokine, has various homeostatic and pathogenic bioactivities. The aim of this study was to assess the neuroprotective effect of ketamine against TNF‐α‐induced motor dysfunction and neuronal necroptosis in male C57BL/6J mice in vivo and HT‐22 cell lines in vitro. The behavioural testing results of the present study indicate that ketamine ameliorated TNF‐α‐induced neurological dysfunction. Moreover, immunohistochemical staining results showed that TNF‐α‐induced brain dysfunction was caused by necroptosis and microglial activation, which could be attenuated by ketamine pre‐treatment inhibiting reactive oxygen species production and mixed lineage kinase domain‐like phosphorylation in hippocampal neurons. Therefore, we concluded that ketamine may have neuroprotective effects as a potent inhibitor of necroptosis, which provides a new theoretical and experimental basis for the application of ketamine in TNF‐α‐induced necroptosis‐associated diseases.