Glymphatic–meningeal lymphatic system imbalance: a peripheral-to-central inflammatory bridge in perioperative neurocognitive disorders

Perioperative neurocognitive disorders (PNDs) are common postoperative complications, particularly in elderly patients. While surgical trauma is known to trigger systemic inflammation, the mechanisms linking peripheral immune activation to perioperative neurocognitive dysfunction remain not fully elucidated. The glymphatic-meningeal lymphatic system is crucial for maintaining homeostasis because it facilitates the exchange of cerebrospinal fluid and interstitial fluid, clears metabolic waste, and eliminates immune mediators. Recent studies have indicated that dysfunction of this clearance axis may contribute to the exacerbation of PNDs. This article explores how perioperative inflammation may influence the glymphatic-meningeal lymphatic system, thereby promoting neuroinflammation. We propose that the interplay between the inflammatory burden and the clearance capacity of the brain is a critical factor in the pathogenesis of PNDs. Through multimodal approaches-integrating advanced imaging techniques, high-dimensional immunogenomic profiling, biofluid biomarkers, and neurophysiological monitoring-we can more comprehensively characterize alterations in glymphatic-meningeal lymphatic function and their interactions with microcirculatory and immune dynamics. Furthermore, we discuss potential therapeutic strategies targeting the glymphatic-meningeal lymphatic system, which could offer clinical insights for the prevention and treatment of PNDs by targeting the underlying mechanisms.