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Elevated levels of homocysteine compromise blood-brain barrier integrity in mice

Atul F Kamath1, Anil K Chauhan, Janka Kisucka

  • 1CBR Institute for Biomedical Research, 800 Huntington Ave, Boston, MA 02115, USA.

Blood
|September 29, 2005
PubMed

Insights

Elevated homocysteine (Hcy) damages brain microvessels and increases blood-brain barrier permeability. This research links high Hcy to vascular issues in the brain, potentially connecting cardiovascular and Alzheimer diseases.

Area of Science:

  • Neuroscience
  • Cardiovascular Science
  • Biochemistry

Background:

  • Elevated plasma homocysteine (Hcy) is linked to increased risks of cardiovascular disease and Alzheimer disease.
  • A potential vascular connection between these conditions remains to be fully elucidated.

Purpose of the Study:

  • To investigate the impact of elevated Hcy on the blood-brain barrier (BBB).
  • To explore the role of Hcy in cerebrovascular dysfunction.

Main Methods:

  • Utilized cystathionine beta-synthase (Cbs)-heterozygous mice on a hyperhomocysteinemic diet.
  • Employed intravital microscopy to analyze leukocyte-endothelial interactions in mesenteric venules.
  • Quantified BBB permeability using Evans blue dye in brain tissue.

Main Results:

  • Hyperhomocysteinemic mice exhibited reduced leukocyte rolling velocity and increased leukocyte adhesion.
  • Increased P-selectin expression was observed in mutant mice.
  • BBB permeability was significantly elevated by 25% in the cortex of Cbs(+/-) mice compared to wild-type controls.

Conclusions:

  • Elevated Hcy exerts a toxic effect on brain microvessels.
  • Hcy is implicated in the disruption of the blood-brain barrier integrity.
  • This finding suggests a potential mechanism linking hyperhomocysteinemia to neurological disorders.

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