Opening of the Blood-Brain Barrier before Cerebral Pathology in Mild Hyperhomocysteinemia

摘要: Hyperhomocysteinemia (HHcy) is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern cerebral pathology in mouse model mild HHcy, because understanding time course provides basis mechanisms involved. C57Bl/6 mice with heterozygous deletion cystathionine β-synthase (cbs+/−; Het) were used as HHcy along their wild-type littermates (cbs+/+; WT). Mice ‘young’ (5.3±0.2 months age) and ‘old’ (16.6±0.9 age). Blood-brain barrier (BBB) permeability quantified from Evans blue sodium fluorescein extravasation. Microvascular architecture assessed by z-stack confocal microscopy. Leukoaraiosis measured Luxol fast stained slides paraffin brain sections. Inflammation using standard antibody-based immunohistochemical techniques. Cognitive function Morris water maze. BBB significantly greater Het vs. WT at all ages (p<0.05). There no differences microvascular among groups. Compared other groups, old had leukoaraiosis, inflammation fornix, impairment In increased precedes onset pathology. This new paradigm may play role progression disease HHcy.