Abstract The glymphatic system has emerged as a critical regulator of central nervous system homeostasis, governing cerebrospinal fluid–interstitial fluid exchange, metabolic waste clearance, and brain water balance. Accumulating experimental and human data increasingly implicate glymphatic dysfunction in the pathogenesis of stroke and cerebral small vessel disease (CSVD), where impaired clearance amplifies oedema formation, neuroinflammation, and long-term cognitive decline. This narrative review synthesizes contemporary mechanistic insights into glymphatic regulation, with a focus on aquaporin-4 (AQP4) polarization, vascular–astrocytic coupling, and inflammatory signaling. We critically appraise translational neuroimaging advances, highlighting clinically relevant applications of diffusion tensor imaging along the perivascular space (DTI-ALPS) in human cohorts linking CSVD burden, sleep disruption, and cognitive impairment. Emerging therapeutic strategies including focused ultrasound with microbubbles, AAV-mediated gene therapy targeting AQP4, and surgical modulation of cervical lymphatic outflow are discussed alongside lifestyle-based interventions. Collectively, current evidence positions the glymphatic system not merely as a biomarker of cerebrovascular injury, but as a dynamic and potentially modifiable therapeutic target in stroke and CSVD.
Chavda et al. (Thu,) studied this question.