CD22 Blockade Alleviates Anesthesia Surgery-Mediated Cognitive Impairment in Aged Mice

Postoperative cognitive dysfunction (POCD) is a common complication characterized by cognitive decline following surgery, with neuroinflammation serving as a critical pathogenic mechanism. Emerging evidence indicates that CD22, an inhibitory receptor primarily expressed on B cells and microglia, plays a key immunomodulatory role in the central nervous system. This study aims to investigate the role of CD22 in mitigating neuroinflammation and ameliorating POCD. Using a murine model of sterile laparotomy, we observed that surgery-induced cognitive impairment was associated with exacerbated hippocampal inflammation and enhanced microglial activation. In contrast, upregulation or agonism of CD22 signaling significantly reduced the release of pro-inflammatory cytokines, including TNF-α and IL-1β, and suppressed microglial overactivation. Notably, CD22-modulated mice exhibited markedly improved performance in behavioral tests assessing learning and memory compared to control groups. Our findings demonstrate that CD22 activation confers protection against POCD by inhibiting surgery-induced neuroinflammation through the S100a9 signaling pathway. Therefore, targeting the CD22 pathway may represent a promising therapeutic strategy for the prevention or treatment of postoperative cognitive dysfunction.