Blood-brain barrier dysfunction in surgery and anesthesia: a potential mechanistic contributor to postoperative cognitive dysfunction.

The blood-brain barrier (BBB) is essential for maintaining central nervous system homeostasis by regulating selective permeability and protecting neural tissue. Surgical interventions and anesthesia can compromise BBB integrity, particularly in elderly patients, contributing to postoperative cognitive dysfunction (POCD). This narrative review provides a BBB-centered perspective on postoperative cognitive dysfunction by critically evaluating blood-brain barrier dysfunction as a potential unifying mechanistic pathway linking surgical stress, systemic inflammation, anesthetic exposure, neuroinflammation, and cognitive decline. While previous reviews have examined these perioperative factors individually, this review integrates current experimental and clinical evidence to highlight BBB disruption as a central contributor to postoperative neurocognitive impairment and discusses its translational implications for perioperative neuroprotection. Surgical trauma triggers an acute inflammatory response with elevated cytokines, increasing BBB permeability and facilitating the entry of neurotoxic substances into the brain, thereby promoting neuroinflammation. Anesthetic agents may further exacerbate these effects. Emerging evidence suggests that BBB dysfunction may represent an important mechanistic contributor linking perioperative stress, neuroinflammation, and cognitive impairment; however, direct evidence establishing causality in humans remains limited. Interventions targeting BBB stabilization and perioperative neuroprotection may represent promising strategies to reduce the risk of POCD. A better understanding of these mechanisms is crucial for developing strategies to preserve cognitive function and improve postoperative outcomes. However, much of the current evidence is derived from preclinical studies, and direct causal relationships in humans remain limited. Future research should clarify neuroinflammatory pathways and identify effective protective therapies.