1. Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, P. R. China.
2. Department of Anesthesiology, The First Affiliated Hospital of Chengdu Medical College, Xindu, Sichuan, 610500, P. R. China.
*Co-first authors with equal contributions to this work.
Recent mounting studies showed that neuroinflammation caused by surgery or anesthesia is closely related to postoperative cognitive dysfunction (POCD). This study investigated the effect of mineralocorticoid receptor (MR) on neuroinflammation and POCD. To detect the MR effect in an animal model, we randomly divided rats into control, anesthesia, and surgery groups. To determine whether the MR-specific blocker eplerenone (EPL) could improve cognitive dysfunction, we assigned other animals into the control, surgery and EPL treatment, and surgery groups. Cognitive function was detected using the Morris water maze. Serum cytokine levels were measured by ELISA, and the histopathological changes of hippocampal neurons were identified by hematoxylin/eosin and Nissl staining. Our research confirmed that anesthesia and surgical stimulation could lead to IL-1β, IL-6, and TNF-α activation and hippocampal neuronal degeneration and pathological damage. MR was upregulated in the hippocampus under cognitive impairment condition. Additionally, EPL could alleviate inflammatory activation and neuronal damage by exerting neuroprotective effects. The preclinical model of sevoflurane anesthesia/splenectomy implied that MR expression is upregulated by regulating the neuroinflammation in the brain under POCD condition. Manipulating the MR expression by EPL could improve the inflammation activation and neuronal damage.
Keywords: Mineralocorticoid receptor, Cognitive decline, Postoperative cognitive dysfunction, Eplerenone, Neuroinflammation