Post-stroke glymphatic and meningeal lymphatic dysfunction: mechanisms, imaging evidence, and translational...

Stroke may disrupt brain fluid and waste clearance pathways, including the glymphatic and meningeal lymphatic systems, across ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. This review synthesizes current evidence on post-stroke alterations in these pathways, with emphasis on subtype-specific mechanisms, the distinction between experimental and human evidence, and the strengths and limitations of available imaging approaches. Experimental studies suggest that ischemic stroke may involve hyperacute perivascular cerebrospinal fluid influx followed by impaired glymphatic transport, that intracerebral hemorrhage is more closely linked to blood-product-related disruption of glymphatic and meningeal lymphatic drainage, and that subarachnoid hemorrhage may involve combined glymphatic and meningeal lymphatic failure. We further review in vivo imaging methods, particularly magnetic resonance imaging (MRI) approaches such as dynamic contrast-enhanced MRI, diffusion tensor image analysis along the perivascular space, and structural perivascular space imaging, and we discuss their biological directness and translational limitations. Across modalities, the most direct evidence still comes mainly from experimental tracer-based MRI and selected intrathecal contrast-enhanced MRI studies in humans. Among stroke subtypes, subarachnoid hemorrhage currently provides the most direct human MRI evidence of combined clearance-pathway dysfunction, whereas most other human stroke data rely on indirect surrogate markers, especially diffusion tensor image analysis along the perivascular space. Accordingly, current clearance-pathway imaging should be regarded primarily as a mechanistic and early translational research tool rather than a validated clinical biomarker. Importantly, most proposed links between molecular mechanisms, imaging readouts, and clinical outcomes remain inferential and require prospective validation in human stroke cohorts. Prospective human studies are needed to test whether targeting brain clearance pathways improves post-stroke recovery and cognition.