Premium
Stabilization of blood‐brain barrier by caffeine in cholesterol‐fed rabbits
Author(s) -
Chen Xuesong,
Ghribi Othman,
Geiger Jonathan D.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1168-d
Subject(s) - caffeine , occludin , blood–brain barrier , tight junction , extravasation , inflammation , cholesterol , medicine , endocrinology , pharmacology , chemistry , immunology , central nervous system , biochemistry
Blood‐brain barrier (BBB) is essential for brain homeostasis, and once disrupted can contribute to a variety of neurological disorders. Recent epidemiological and experimental studies indicate that caffeine, when ingested chronically, is protective against a number of neurological disorders, but by poorly understood mechanisms. In this study, we tested the hypothesis that chronic ingestion of caffeine protects against disruption of BBB. New Zealand rabbits were fed with a 2% cholesterol‐enriched diet, and caffeine was administered at doses of either 3 mg or 30 mg in drinking water daily for 12 weeks. Perfused brains were evaluated for BBB leakage, tight junction protein expression, and vascular inflammation by immunostaining and immunoblotting techniques. We found that caffeine blocked cholesterol‐enriched diet induced increases in extravasation of IgG and fibrinogen, evidence for BBB leakage. Cholesterol‐fed rabbits exhibited 10‐fold increases in levels of plasma cholesterol, and this was not affected by caffeine. Caffeine blocked cholesterol‐enriched diet induced decreases in levels of occludin, claudin‐1 and ZO‐1, tight junction proteins, and increases in expression of VCAM‐1 and RAGE, markers for vascular inflammation. Our results suggest that caffeine stabilizes BBB by inhibiting vascular inflammation. (Supported by P20 RR‐017699 from the NCRR, a component of the NIH)