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 Blood, 15 January 2006, Vol. 107, No. 2, pp. 591-593.
Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-06-2506.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Brief report

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

Atul F. Kamath, Anil K. Chauhan, Janka Kisucka, Vandana S. Dole, Joseph Loscalzo, Diane E. Handy, and Denisa D. Wagner

From the CBR Institute for Biomedical Research, Boston; Department of Pathology, Harvard Medical School, Boston; and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Elevated levels of plasma homocysteine (Hcy) correlate with increased risk of cardiovascular and Alzheimer diseases. We studied the effect of elevated Hcy on the blood-brain barrier (BBB) to explore the possibility of a vascular link between the 2 diseases. On a hyperhomocysteinemic diet, cystathionine beta-synthase (Cbs)–heterozygous mice develop hyperhomocysteinemia. Intravital microscopy analysis of the mesenteric venules showed that leukocyte rolling velocity was markedly decreased and numbers of adherent cells were increased in the mutant mice. This was due at least in part to increased expression of P-selectin. BBB permeability was measured by Evans blue dye permeation and was found to be 25% greater in the Cbs+/– cortex compared with wild-type controls. Our study suggests an important toxic effect of elevated Hcy on brain microvessels and implicates Hcy in the disruption of the BBB.


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