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Updated: Aug 19, 2026
Acupuncture Treatment in a Mouse Model of Chronic Hypoxia-Induced Cognitive Dysfunction
Published on: December 8, 2023
Role of NRF2 in Electroacupuncture's Effects on Postoperative Cognitive Impairment in Rats
Zhi-Gang Wang1, Dong-Ran Cui1, Yi Gao2
1Department of Anesthesiology, Handan Central Hospital, Handan, People's Republic of China.
Objective:
Postoperative cognitive dysfunction (POCD), characterized by cognitive and memory decline following anesthesia and surgery, is a common complication in elderly patients. Nuclear factor erythroid-derived 2-like 2 (NRF2), a key regulator of cellular redox balance, has been implicated in cognitive processes in various neurological disorders. Electroacupuncture (EA), with its controllable stimulation parameters, has shown preventive effects against cognitive dysfunction. This study aimed to investigate whether NRF2 mediates the beneficial effects of EA on cognitive function in POCD.
Methods:
A POCD model was established in 20-month-old male Sprague-Dawley rats undergoing tibial fracture surgery. Beginning on postoperative day 24, EA was administered at the Hegu (LI4), Neiguan (PC6), and Zusanli (ST36) acupoints once daily for five consecutive days. The specific NRF2 antagonist ML385 (30 mg/kg) was intraperitoneally administered 2 hours before each EA session over the same period. Behavioral tests, including the T-maze test, fear conditioning (FC), and novel object recognition (NOR), were conducted on postoperative day 30. Immunofluorescence staining was used to assess neuronal count, apoptosis, microglial activation, and the percentage of NRF2-positive microglia. Electrophysiological recordings of brain activity were also performed.
Results:
EA treatment significantly improved cognitive and memory performance in POCD rats. Immunofluorescence analysis revealed reduced neuronal apoptosis, increased synaptic density, suppressed microglial activation, and enhanced nuclear translocation of NRF2, indicating attenuated neuroinflammation and oxidative stress. Furthermore, EA strengthened the phase-amplitude coupling between theta and gamma oscillations. Notably, all these neuroprotective and cognitive-enhancing effects of EA were abolished by ML385.
Conclusion:
In a POCD rat model, our findings demonstrate that EA ameliorates cognitive impairment, and this effect is potentially mediated through NRF2 pathway activation.