Elevated levels of homocysteine compromise blood-brain barrier integrity in mice
| Autor: | Atul F. Kamath, Anil K. Chauhan, Janka Kisucka, Denisa D. Wagner, Vandana S. Dole, Diane E. Handy, Joseph Loscalzo |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Hyperhomocysteinemia Heterozygote Homocysteine Immunology Cystathionine beta-Synthase Blood–brain barrier Biochemistry Hemostasis Thrombosis and Vascular Biology Microcirculation chemistry.chemical_compound Mice Internal medicine medicine Cell Adhesion Leukocytes Animals Evans Blue Mice Knockout Venule biology Brain Cell Biology Hematology medicine.disease Cystathionine beta synthase Diet Up-Regulation Mice Inbred C57BL P-Selectin Endocrinology medicine.anatomical_structure chemistry Blood-Brain Barrier biology.protein Intravital microscopy |
| Zdroj: | Blood. 107(2) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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