Related Experiment Video
Updated: Nov 23, 2025
Author Spotlight: Improving Anesthesia Protocols for Enhanced Mouse Acupuncture Research
Published on: December 8, 2023
Blocking the Mineralocorticoid Receptor Improves Cognitive Impairment after Anesthesia/Splenectomy in Rats
Xixia Feng1, Lu Chen1, Ruihao Zhou1
1Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, P. R. China.
Abstract:
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.
Insights
Surgery and anesthesia can cause neuroinflammation, leading to postoperative cognitive dysfunction (POCD). Blocking the mineralocorticoid receptor (MR) with eplerenone (EPL) reduced inflammation and protected against POCD in rats.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Neuroinflammation, triggered by surgery or anesthesia, is increasingly linked to postoperative cognitive dysfunction (POCD).
- The role of the mineralocorticoid receptor (MR) in mediating these effects remains to be fully elucidated.
- Understanding the mechanisms underlying POCD is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the influence of the mineralocorticoid receptor (MR) on neuroinflammation and cognitive function following surgical procedures.
- To evaluate the potential of the MR-specific blocker, eplerenone (EPL), in mitigating neuroinflammation and improving cognitive deficits.
- To explore the relationship between MR expression, inflammatory markers, and neuronal damage in a rat model of POCD.
Main Methods:
- Rats were subjected to anesthesia and/or surgery, with separate groups receiving eplerenone (EPL) treatment.
- Cognitive function was assessed using the Morris water maze test.
- Serum cytokine levels (IL-1β, IL-6, TNF-α) were quantified via ELISA, and hippocampal neuronal histology was examined using H&E and Nissl staining.
Main Results:
- Anesthesia and surgery induced significant increases in IL-1β, IL-6, and TNF-α, alongside hippocampal neuronal degeneration and damage.
- Mineralocorticoid receptor (MR) expression was found to be upregulated in the hippocampus under conditions of cognitive impairment.
- Eplerenone (EPL) treatment effectively attenuated inflammatory markers and neuronal damage, demonstrating neuroprotective effects.
Conclusions:
- Anesthesia and surgical stress promote neuroinflammation and neuronal damage, contributing to postoperative cognitive dysfunction (POCD).
- Mineralocorticoid receptor (MR) upregulation plays a key role in the neuroinflammatory response associated with POCD.
- Pharmacological inhibition of MR with eplerenone (EPL) offers a promising therapeutic approach to alleviate neuroinflammation and protect against cognitive decline.
