Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease
| Autor: | Jonathan D. Geiger, Othman Ghribi, Xuesong Chen, John F. Wagener, Jeremy W. Gawryluk |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Immunology Biology Blood–brain barrier Occludin lcsh:RC346-429 High cholesterol Tight Junctions Random Allocation 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Caffeine Internal medicine medicine Animals lcsh:Neurology. Diseases of the nervous system 030304 developmental biology 0303 health sciences Dose-Response Relationship Drug Microglia Cholesterol Research General Neuroscience Fibrinogen Membrane Proteins medicine.disease Extravasation Diet 3. Good health Disease Models Animal medicine.anatomical_structure Endocrinology Neurology Biochemistry chemistry Blood-Brain Barrier Astrocytes Immunoglobulin G Central Nervous System Stimulants Rabbits Alzheimer's disease 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 5, Iss 1, p 12 (2008) |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/1742-2094-5-12 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|