Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease

• Published in: Journal of neuroinflammation 2008-04, Vol.5 (1), p.12-12, Article 12
• Main Authors: Chen, Xuesong, Gawryluk, Jeremy W, Wagener, John F, Ghribi, Othman, Geiger, Jonathan D
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Analysis; Animals; Astrocytes - drug effects; Astrocytes - pathology; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; Caffeine; Caffeine - blood; Caffeine - pharmacology; Care and treatment; Central Nervous System Stimulants - blood; Central Nervous System Stimulants - pharmacology; Cholesterol - administration & dosage; Cholesterol - adverse effects; Cholesterol - pharmacology; Development and progression; Diet; Disease Models, Animal; Dosage and administration; Dose-Response Relationship, Drug; Fibrinogen - metabolism; Health aspects; Immunoglobulin G; Immunoglobulin G - metabolism; Membrane Proteins - metabolism; Microglia - drug effects; Microglia - pathology; Occludin; Physiological aspects; Prevention; Rabbits; Random Allocation; Tight Junctions - drug effects; Tight Junctions - metabolism; Tight Junctions - pathology
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/1742-2094-5-12

High levels of serum cholesterol and disruptions of the blood brain barrier (BBB) have all been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease. Results from studies conducted in animals and humans suggest that caffeine might be protective against Alzheimer's disease but by poorly understood mechanisms. Using rabbits fed a cholesterol-enriched diet, we tested our hypothesis that chronic ingestion of caffeine protects against high cholesterol diet-induced disruptions of the BBB. New Zealand rabbits were fed a 2% cholesterol-enriched diet, and 3 mg caffeine was administered daily in drinking water for 12 weeks. Total cholesterol and caffeine concentrations from blood were measured. Olfactory bulbs (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, BBB tight junction protein expression levels, activation of astrocytes, and microglia density using histological, immunostaining and immunoblotting techniques. We found that caffeine blocked high cholesterol diet-induced increases in extravasation of IgG and fibrinogen, increases in leakage of Evan's blue dye, decreases in levels of the tight junction proteins occludin and ZO-1, increases in astrocytes activation and microglia density where IgG extravasation was present. Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the BBB, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease.