Clinical and preclinical evidence of meningeal immunity and glymphatic pathways in stroke: a systematic review.

Glymphatic transport, meningeal lymphatic drainage, and meningeal immunity have been implicated in metabolic waste clearance, cerebral edema formation, and the regulation of neuroinflammation after stroke. However, the available evidence remains fragmented and has not been systematically integrated. This review was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, the Cochrane Library, and Web of Science were searched from database inception to April 3, 2026, for studies investigating glymphatic pathways, the meningeal lymphatic system, meningeal immune responses, and related imaging biomarkers in patients with clinical stroke or in experimental stroke models. Two investigators independently screened studies, extracted data, and assessed study quality. Because of substantial heterogeneity in study design, imaging methodology, experimental models, and outcome measures, findings were synthesized narratively. A total of 64 studies were included, comprising 17 clinical studies and 47 preclinical studies. Clinical studies, which were largely based on MRI-derived glymphatic imaging biomarkers, suggest that glymphatic dysfunction is associated with stroke severity, cognitive impairment, and clinical outcomes. Preclinical evidence indicates that AQP4 dysregulation, impaired meningeal lymphatic drainage, and border-associated immune activation may influence waste clearance, cerebral edema, inflammation, and tissue repair after stroke. Future studies should establish standardized imaging frameworks, conduct prospective longitudinal validation, define mechanistic differences across stroke subtypes, and facilitate the translation of targeted interventions. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/home, identifier CRD420261359988.