Carnosine ameliorates postoperative cognitive dysfunction of aged rats by limiting astrocytes pyroptosis

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.