Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients, and
neuroinflammation is a key hallmark. Recent studies suggest that the
NOD-like receptor family, pyrin domain containing 3 (NLRP3)
inflammasome-mediated astrocytes pyroptosis is involved in the regulation of
neuroinflammation in many neurocognitive diseases, while its role in POCD remains obscure.
Carnosine is a natural endogenous
dipeptide with anti-inflammatory and
neuroprotective effects. To explore the effect of
carnosine on POCD and its mechanism, we established a POCD model by exploratory
laparotomy in 24-month-old male Sprague-Dawley rats. We found that the administrated of
carnosine notably attenuated surgery-induced NLRP3
inflammasome activation and pyroptosis in astrocytes, central
inflammation, and neuronal damage in the hippocampus of aged rats. In addition,
carnosine dramatically ameliorated the learning and
memory deficits of surgery-induced aged rats. Then in the in vitro experiments, we stimulated primary astrocytes with
lipopolysaccharide (LPS) after
carnosine pretreatment. The results also showed that the application of
carnosine alleviated the activation of the NLRP3
inflammasome, pyroptosis, and inflammatory response in astrocytes stimulated by LPS. Taken together, these findings suggest that
carnosine improves POCD in aged rats via inhibiting NLRP3-mediated astrocytes pyroptosis and
neuroinflammation.