Neuroinflammation-driven glymphatic dysfunction: implications for disease progression and drug-based modulation

The glymphatic system plays a critical role in central nervous system waste clearance, and its impairment is increasingly linked to neuroinflammation and accelerated disease progression. The latest 2025 evidence reveals that inflammatory microglial activation, perivascular aquaporin-4 disorganization, and impaired cerebrospinal fluid-interstitial fluid exchange contribute to dysfunctional neuro-clearance, fostering protein aggregation and neuronal injury. Emerging data also highlight the potential for drug-mediated modulation of glial metabolism, vascular inflammation, and aquaporin-4 stability to support early neuro-barrier protection and glymphatic flow recovery.