Elevated Levels of Homocysteine Compromise Blood-Brain Barrier Integrity in Mice
| Autor: | Denisa D. Wagner, Diane E. Handy, Joseph Loscalzo, Vandana S. Dole, Janka Kisucka, Atul F. Kamath, Anil K. Chauhan |
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| Rok vydání: | 2005 |
| Předmět: | |
| Zdroj: | Blood. 106:3856-3856 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v106.11.3856.3856 |
| Popis: | Elevated levels of plasma homocysteine (Hcy) correlate with increased risks of cardiovascular and Alzheimer’s diseases. We studied the effect of elevated Hcy on the blood-brain barrier (BBB) to explore the possibility of a vascular link between the two diseases. On a methionine-enriched diet, cystathionine beta-synthase (CBS) heterozygous mice develop hyperhomocysteinemia (HHcy). To evaluate the extent of HHcy induced by an 8-week methionine-enriched diet (Diet), we determined plasma Hcy concentration. Concentrations were 23.5 ± 5 μM for wild type (WT) and 98.4 ± 22 μM for CBS+/− on Diet and 4.1 ± 0.20 μM for WT on normal chow. Inflammation can lead to BBB breakdown, therefore we first determined whether we could detect systemic endothelial activation/increased leukocyte adherence in the CBS+/− mice as an indicator of inflammation. We observed mesenteric venules (200–300 μm) in WT and CBS +/− mice fed Diet and compared them with WT on chow. Leukocyte rolling velocity was slower in CBS+/− than in WT mice indicating an increase in the density of adhesion molecules on the endothelium. In CBS+/− mice, 60% of leukocytes rolled at a velocity of < 10 μm/s as compared with only 8% in WT mice on Diet (P |
| Databáze: | OpenAIRE |
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