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Opening of the Blood-Brain Barrier Before Cerebral Pathology in Mild Hyperhomocysteinemia
PLoS ONE (2013)
  • Bryce C. Rhodehouse, Idaho State University
  • Jamie N. Mayo, Idaho State University
  • Richard S. Beard, Jr., Idaho State University
  • Cheng-Hung Chen, Idaho State University
  • Shawn E. Bearden, Idaho State University
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<sup>+/-</sup>; Het) were used as a model of mild HHcy along with their wild-type littermates (cbs<sup>+/+</sup> ; 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<0.05). There were no differences in microvascular architecture among the groups. Compared with all other groups, old Het mice had significantly greater leukoaraiosis, inflammation in the fornix, and cognitive impairment (p<0.05). In mild HHcy, increased permeability of the BBB precedes the onset of cerebral pathology. This new paradigm may play a role in the progression of disease in HHcy.
  • cognitive impairment,
  • mouse models,
  • learning,
  • swimming,
  • fluorescence,
  • blood-brain barrier permeability assay
Publication Date
May, 2013
Publisher Statement
This document was originally published in PLoS ONE by the Public Library of Science. This work is provided under a Creative Commons Attribution 4.0 license. Details regarding the use of this work can be found at: doi: 10.1371/journal.pone.0063951
Citation Information
Bryce C. Rhodehouse, Jamie N. Mayo, Richard S. Beard, Cheng-Hung Chen, et al.. "Opening of the Blood-Brain Barrier Before Cerebral Pathology in Mild Hyperhomocysteinemia" PLoS ONE Vol. 8 Iss. 5 (2013) p. e63951-1 - e63951-7
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This work is licensed under a Creative Commons CC_BY International License.