High-frequency rTMS improves post-stroke cognitive impairment and is associated with region-specific BBB remodeling and increased pericyte coverage

Post-stroke cognitive impairment (PSCI) remains without effective disease-modifying therapies. Repetitive transcranial magnetic stimulation (rTMS) is a promising noninvasive intervention, but whether its beneficial effects are associated with blood-brain barrier (BBB) remodeling and pericyte coverage remains unclear. In this study, adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion (tMCAO) or sham surgery. Beginning on post-operative day 7, tMCAO rats received either restraint-only handling or 20-Hz rTMS once daily for 21 consecutive days. Behavioral performance, cerebral blood flow (CBF), infarct volume, BBB leakage, and vascular remodeling were evaluated using behavioral tests, laser speckle imaging, TTC staining, immunofluorescence, and Western blotting. High-frequency rTMS improved cognitive performance and reduced anxiety-like behavior after stroke. These behavioral benefits were accompanied by increased ipsilateral CBF, although infarct volume was not significantly reduced. Moreover, rTMS was associated with partial, region-specific BBB remodeling, including reduced cortical IgG leakage, increased vascular Occludin expression, and enhanced pericyte coverage, particularly in the hippocampus. Evans blue extravasation showed a nonsignificant trend toward reduction. In conclusion, subacute high-frequency rTMS improved behavioral outcomes after stroke and was associated with region-specific BBB remodeling and increased pericyte coverage. These findings suggest that vascular and perivascular remodeling may contribute to the beneficial effects of rTMS in PSCI.