Neuroreport · Apr 30, 2025

Effect of peripheral adiponectin on perioperative neurocognitive disorder via regulation of glucose metabolism in aged rats

By Zhang Z, Hu C, Chi Y et al.

OBJECTIVE: Perioperative neurocognitive disorder (PND) is a significant complication affecting elderly patients after surgery, with limited effective interventions to improve its prognosis yet. We have found that decreased serum adiponectin (APN) and increased cerebrospinal fluid (CSF) lactate are involved in the pathophysiological process of PND in elderly patients. APN is known for its anti-insulin resistance property. In this study, we further explored the regulatory effects of APN on cerebral glucose metabolism in PND rats. METHODS: Twelve-month-old male Sprague-Dawley rats were divided into 3 groups: the sham, PND (splenectomy) and PND+APN (50 mg/kg/day intragastrically) groups. ELISA, quantitative PCR and colorimetric analysis were conducted to analyze tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), pyruvate and lactate in serum, CSF and hippocampus. Open field and Morris water maze (MWM) tests were used to detect hippocampus-dependent cognitive function. Western blot and flow cytometry were conducted to detect neuronal apoptosis in primary hippocampal neurons. RESULTS: In vivo, peripheral APN administration reversed surgery-induced reductions in serum APN expression and elevated levels of cerebral lactate, the ratio of lactate/pyruvate, TNF-α and IL-1β, thereby improving cognitive performance in MWM and Open Field tests. In vitro, APN at concentrations of 2 and 10 ng/ml dose-dependently reduced lipopolysaccharide-induced caspase 3 expression and p38 phosphorylation in neurons, inhibiting apoptosis. CONCLUSIONS: Cerebral hypometabolism is one of the pathogenic mechanisms of PND. APN shows its effects on regulating glucose metabolism to inhibit neuroinflammation and neuronal apoptosis in PND. And the underlying mechanism of APN should be investigated further.

doi.org/10.1097/wnr.0000000000002169PubMed 40377973Interventions