The effects of transcranial magnetic stimulation on the blood-brain barrier and glymphatic clearance: a scoping review with diagnostic and therapeutic implications

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Abstract Background The blood–brain barrier (BBB) prevents most therapeutics from reaching the brain, and the functionally coupled glymphatic system governs solute clearance. A controlled, non-invasive means of modulating these systems would have diagnostic and therapeutic value. We reviewed whether transcranial magnetic stimulation (TMS) affects BBB permeability and glymphatic clearance. Methods In this scoping review, PubMed and Embase were searched from 1985 to June 2026 for studies applying any form of TMS with outcomes relating to the BBB or glymphatic system, in human, animal, or in-vitro models. Direct permeability measures, glymphatic measures (including DTI-ALPS), and indirect serum markers were eligible. ClinicalTrials.gov was searched for ongoing trials. Results Forty-five studies were included and grouped into six categories by outcome system and direction of effect. Three main effects emerged. First: single-session, low-frequency rTMS at threshold or supra-threshold intensity produced immediate, focal, dose-dependent BBB opening that reversed within minutes to hours, facilitating delivery of small and large molecules. Second: repeated high-frequency, multi-session protocols were associated with barrier stabilisation and repair in injury models. Third, similar multi-session protocols were associated with enhanced glymphatic and meningeal-lymphatic clearance. Human evidence rested largely on indirect surrogates (ADC, DTI-ALPS, S100B, neuron-specific enolase), with only one study using sensitive contrast-based imaging to demonstrate opening. A further twelve studies using alternative magnetic platforms mapped the field’s conceptual boundary. Conclusions TMS may induce controlled, transient, reversible BBB opening and longer-term protective and clearance effects, but human data remain limited, warranting dedicated validation and safety characterisation.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.