Esketamine improves propofol-induced brain injury and cognitive impairment in rats

As an intravenous anesthetic, propofol has been indicated to induce neurotoxicity in both animal and human brains. It is of great significance to better understand the potential mechanism of propofol-induced neurotoxicity to eliminate the side effects of propofol. Esketamine is a sedative that has been proven to have an antidepressant effect. However, its effect on propofol-induced neurotoxicity and the underlying mechanism remain unclear. Herein, we investigated the role of esketamine in propofol-induced brain injury. A rat model of propofol-induced brain injury was established with or without the treatment of esketamine. The results demonstrated that propofol-induced impairment in spatial learning and memory of rats and promoted oxidative stress, neuronal injury and apoptosis in rat hippocampal tissues. The effects caused by propofol were attenuated by esketamine. Esketamine activated the mature brain-derived neurotrophic factor/tropomyosin receptor kinase B/phosphatidylinositide 3-kinase (mBDNF/TrkB/PI3K) signaling pathway in propofol-administrated rats. Moreover, knocking down BDNF partially reversed esketamine-mediated activation of the mBDNF/TrkB/PI3K signaling pathway and inhibition of neuronal apoptosis in propofol-induced rats. Overall, esketamine mitigates propofol-induced cognitive dysfunction and brain injury in rats by activating mBDNF/TrkB/PI3K signaling.

Automated summary

Propofol, an intravenous anesthetic, induces neurotoxicity, but esketamine can attenuate propofol-induced brain injury and cognitive dysfunction by activating the mBDNF/TrkB/PI3K signaling pathway.