Opening of the blood-brain barrier before cerebral pathology in mild hyperhomocysteinemia

Hyperhomocysteinemia (HHcy) is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern of cerebral pathology in a mouse model of mild HHcy, because understanding this time course provides the basis for understanding the mechanisms involved. C57Bl/6 mic...

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Bibliographic Details
Published in:PloS one 2013-05, Vol.8 (5), p.e63951-e63951
Main Authors: Rhodehouse, Bryce C, Mayo, Jamie N, Beard, Jr, Richard S, Chen, Cheng-Hung, Bearden, Shawn E
Format: Article
Language:English
Subjects:
Age
Analysis
Animal cognition
Animals
Apoptosis
Architecture
Autophagy
Biology
Blood-brain barrier
Blood-Brain Barrier - pathology
Blood-Brain Barrier - physiopathology
Brain
Brain - pathology
Brain - physiopathology
Cell death
Cognitive ability
Confocal microscopy
Cystathionine beta-Synthase - genetics
Cystathionine beta-Synthase - metabolism
Disease Models, Animal
Enzymes
Evans Blue - chemistry
Extravasation
Fluorescein
Fornix
Homocysteine
House mouse
Hyperhomocysteinemia
Hyperhomocysteinemia - pathology
Hyperhomocysteinemia - physiopathology
Hypertension
Impairment
Laboratory animals
Leukoaraiosis
Leukoaraiosis - pathology
Male
Medicine
Membrane permeability
Mice
Mice, Inbred C57BL
Microscopy
Microscopy, Confocal
Microvasculature
Mutation
Paraffin
Pathology
Permeability
Risk factors
Rodents
Sodium
Stroke
Systematic review
Vitamin deficiency
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Summary:Hyperhomocysteinemia (HHcy) is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern of cerebral pathology in a mouse model of mild HHcy, because understanding this time course provides the basis for understanding the mechanisms involved. C57Bl/6 mice with heterozygous deletion cystathionine β-synthase (cbs (+/-); Het) were used as a model of mild HHcy along with their wild-type littermates (cbs (+/+); WT). Mice were 'young' (5.3±0.2 months of age) and 'old' (16.6±0.9 months of age). Blood-brain barrier (BBB) permeability was quantified from Evans blue and sodium fluorescein extravasation. Microvascular architecture was assessed by z-stack confocal microscopy. Leukoaraiosis was measured from Luxol fast blue stained slides of paraffin brain sections. Inflammation was quantified using standard antibody-based immunohistochemical techniques. Cognitive function was assessed using the Morris water maze. BBB permeability was significantly greater in Het vs. WT mice at all ages (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0063951