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Updated: Oct 16, 2026
Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
Longitudinal quantitative MRI of blood-brain barrier leakage in chronic cerebral hypoperfusion rat model
Ana Sampedro-Viana1, Sabela Fernández-Rodicio1, José Castillo1
1Neuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña, Spain.
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.
