EXPRESS: Longitudinal Quantitative MRI of Blood-Brain Barrier Leakage in Chronic Cerebral Hypoperfusion Rat model.

Abstract

Objective-Methods:Chronic cerebral-hypoperfusion is a key contributor to vascular cognitive impairment, with blood-brain barrier (BBB) dysfunction proposed as an early driver of white matter injury. The temporal-evolution and regional-heterogeneity of BBB-leakage remain poorly characterized in vivo. We longitudinally assessed BBB permeability in Sprague-Dawley rats subjected to bilateral-common carotid artery occlusion (2VO) versus sham controls using contrast-enhanced T1-weighted MRI 9.4T over 12-weeks. Gadolinium-leakage maps were generated and analyzed in predefined regions (cortex, hippocampus, striatum, corpus callosum). Exploratory histological observations included GFAP immunostaining, and circulating biochemical biomarkers (sTWEAK, MMP-9, GOT, cytokines) were quantified.Results:Localized BBB disruption was observed at weeks 3, 6 post-2VO and progressed heterogeneously, with pronounced leakage strictly targeted toward corpus callosum, hippocampus and striatum. Despite descriptive trends showing increased astroglial activation, systemic biochemical biomarkers did not correlate with imaging-derived central BBB-leakage. Volumetric analysis revealed subtle but significant brain atrophy (18% whole-brain reduction) preceding overt T2-signal abnormalities. In the 2VO model studied, BBB dysfunction in chronic-hypoperfusion appears to be a dynamic, region-specific process.Conclusion:Longitudinal contrast-enhanced MRI detected changes that were not mirrored by the circulating biomarkers studied, suggesting its potential utility as a surrogate endpoint in preclinical studies, which should be confirmed in larger cohorts and complementary models.