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

Elevated levels of plasma homocysteine (Hcy) correlate with increased risk of car-diovascular 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 hyperhomo-cysteinemia. Intravital microscopy analy-sis of the mesenteric venules showed that leukocyte rolling velocity was mark-edly 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 permeabil-ity 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 sug-gests an important toxic effect of el-evated Hcy on brain microvessels and implicates Hcy in the disruption of th