Medicarpin Alleviates Isoflurane-Induced Cognitive Dysfunction in Mice by Regulating the BDNF/TrkB Pathway

Postoperative cognitive dysfunction (POCD) seriously threatens elderly surgical patients and has garnered substantial attention in recent years. Anesthesia and/or surgery-induced POCD remains a major issue. This study aimed to evaluate the potential protective effect of medicarpin, a bioactive pterocarpan, against isoflurane-induced cognitive dysfunction. The isoflurane exposure-induced cognitive dysfunction model was established using aged mice. We found that medicarpin reduced isoflurane exposure-induced neuroapoptosis, oxidative stress, endoplasmic reticulum stress, and mitochondrial damage in hippocampal tissues and isoflurane-exposed HT22 cells. We also found that medicarpin prevented the inactivation of BDNF/TrkB pathway in cognitive dysfunction mice and isoflurane-exposed HT22 cells, implying that the neuroprotective effect of medicarpin might be mediated by the BDNF/TrkB signaling. Inhibition of TrkB signaling by K252a attenuated the beneficial effects of medicarpin against isoflurane‑induced neuronal damage in HT22 cells. These findings suggest that medicarpin improves cognitive dysfunction by suppressing neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction via activation of the BDNF/TrkB pathway. The results of this study provide important evidence for developing medicarpin into a potential therapeutic agent for POCD in elderly surgical patients.