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Updated: Jul 14, 2026
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Ononin, a Natural Isoflavone Glycoside, Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Regulating
Ming Li1, Qingmei Peng1, Min Zhu1
1Department of Anesthesiology, the Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Objective:
Postoperative cognitive dysfunction (POCD) is a serious neurological complication that currently lacks effective clinical prevention and treatment. Ononin, a natural isoflavone glycoside, has been confirmed to exhibit potent neuroprotective effects. This study aimed to investigate whether ononin exerts a neuroprotective role against POCD.
Methods:
A POCD model was established in 18 months old mice with unilateral nephrectomy. Ononin (30 mg/kg) was administered intraperitoneally 15 min before surgery. On postoperative Day 3, the Morris water maze and open field tests were used to assess cognitive function. The pathological changes and apoptosis of hippocampal neurons were investigated by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In addition, western blotting and immunofluorescence staining were employed to examine the hippocampal levels of Iba1 and microglial activation. On Days 1 and 3 postsurgery, an enzyme-linked immunosorbent assay (ELISA) was applied to gauge the expression of hippocampal IL-1β, IL-6, and TNF-α. Meanwhile, the levels of hippocampal malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected using the corresponding assay kits.
Results:
We found that anesthesia/surgery induced overt spatial memory deficits and neuronal damage in aged mice. Conversely, ononin pretreatment significantly rescued the pathological process and cognitive impairment. Mechanically, anesthesia/surgery triggered acute increases in hippocampal IL-1β, IL-6, TNF-α, Iba1, and MDA, paralleled by a decline in SOD and GSH levels that was partially reversed by ononin.
Conclusions:
Our findings provide evidence that ononin may ameliorate anesthesia/surgery-induced cognitive deficits through its anti-inflammatory and antioxidant effects, which could be a novel preventive strategy for POCD.
