Post-stroke brain functional reorganization is associated with glymphatic dysfunction during stroke recovery.

Abstract

BACKGROUND: Ischemic stroke may impair glymphatic clearance, but whether this is associated with post-stroke brain functional reorganization in humans remains unclear. METHODS: We prospectively enrolled 48 capsular stroke (CS) patients, 28 pontine stroke (PS) patients, and 50 healthy controls. All participants underwent MRI examinations at baseline (< 7 days) and 90 days post-stroke. Cerebrovascular reactivity (CVR) and the diffusion tensor imaging along the perivascular space (DTI-ALPS) index were measured to assess functional reorganization and glymphatic function. Regions with significant intergroup CVR differences were identified as regions-of-interest (ROIs) reflecting focal functional reorganization. Correlations between ROI-based CVR and DTI-ALPS indices were analyzed to determine which ROIs related to functional reorganization were associated with glymphatic function in CS and PS patients. Cross-lagged panel models (CLPMs) were constructed to analyze the temporal sequence of functional reorganization and glymphatic dysfunction. RESULTS: Both CS and PS patients exhibited focal CVR reorganization and reduced DTI-ALPS indices. Significant associations between CVR and DTI-ALPS indices were found in the putamen and thalamus in both groups. In the putamen, among CS patients, baseline CVR was negatively correlated with both baseline and 90-day ipsilesional hemispheric DTI-ALPS indices (IL.DTI-ALPS) (r = -0.479, p = 0.001; r = -0.493, p < 0.001). In PS patients, baseline contralesional hemispheric DTI-ALPS indices (CL.DTI-ALPS) was negatively correlated with both baseline and 90-day CVR (r = -0.510, p = 0.006; r = -0.532, p = 0.004). Similar patterns of association were observed in the thalamus. Additionally, CLPMs revealed that in CS patients, CVR changes were temporally associated with subsequently reduced DTI-ALPS, while in PS patients, reduced DTI-ALPS were temporally associated with subsequent CVR changes. CONCLUSIONS: Focal CVR reorganization in the putamen and thalamus was associated with post-stroke glymphatic dysfunction in a bidirectional, lesion-location-specific manner. These findings enhance our understanding of post-stroke glymphatic impairment and may help inform strategies to mitigate post-stroke cognitive decline.