The glymphatic system in migraine: A narrative review of emerging mechanisms, glial biomarkers, and diagnostic imaging approaches
Emerging evidence suggests that dysfunction of the glymphatic system, a brain-wide clearance pathway responsible for regulating cerebrospinal and interstitial fluid exchange, plays a meaningful role in migraine pathophysiology. Impaired glymphatic flow may allow inflammatory mediators, metabolic waste products, and vasoactive peptides to accumulate within perivascular and interstitial spaces, promoting trigeminovascular activation, increasing neuronal excitability, and contributing to the progression from episodic to chronic migraine. Glia-derived biomarkers such as aquaporin-4, glial fibrillary acidic protein, and S100B provide important insight into astrocytic polarity, structural integrity, and neuroimmune activation, and may serve as clinically relevant indicators of glymphatic disturbance. Advances in neuroimaging, including diffusion-based analyses along perivascular pathways, quantitative assessment of enlarged perivascular spaces, and emerging fluid-sensitive magnetic resonance imaging techniques, offer noninvasive tools capable of detecting alterations in perivascular transport and microstructural clearance associated with migraine. Although methodological differences across studies require careful interpretation, converging findings indicate that migraine may be characterized not by a single uniform defect, but by heterogeneous patterns of impaired fluid handling and glial dysfunction. Incorporating molecular and imaging biomarkers into future research may improve diagnostic precision and inform therapeutic strategies aimed at restoring glymphatic and perivascular homeostasis.

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