Investigating the Mechanisms of Esketamine in Treating Propofol-Induced Cognitive Impairment in Elderly Rats.
Discovery medicine April 1, 2025 Jieru Zhang, Guofeng Xu, Xiaoli Wang et al.
Esketamine improved cognitive impairment caused by the anesthetic propofol in aged rats. Propofol worsened performance on the water maze and sugar-water preference tests, increased neuronal damage and beta-amyloid deposits, and raised markers of inflammation and apoptosis while reducing autophagy-related proteins and synaptic proteins. Esketamine reversed these effects, including restoring levels of BDNF and ATG-5, and decreasing p-Tau and caspase-3. The findings suggest that esketamine acts by inhibiting the mTOR-BDNF pathway, thereby lifting the suppression of neuronal autophagy and protecting against propofol-induced cognitive dysfunction.