Light and Electron Microscopic Study on the Effect of Caffeine on Blood Brain Barrier Integrity in a Rabbit Model of Alzheimer’s Disease

Introduction: Alzheimer’s disease is the most common neurodegenerative disease associated with aging. Researches have lead to improvements in understanding the underlying biology of this disease. High levels of blood cholesterol and disruption of the blood brain barrier were concerned in pathogenesis of Alzheimer’s disease. Aim of the Work: Was to investigate the blood brain barrier integrity in a rabbit model of Alzheimer’s disease induced by cholesterol enriched diet and the possible protective role of caffeine. Materials and Methods: Forty male rabbits weighing 3 to 4 kg were used and subdivided into 4 groups, ten animals each. Group I was considered the control group. Group II animals received 2% cholesterol-enriched diet for 12 weeks. Group III rabbits received a combination of 2% cholesterol-enriched diet and 3 mg caffeine in 50 ml of drinking water/ day for 12 weeks. Group IV animals received the same dose of caffeine. Three hours before sacrificing the animals, Evan’s blue dye in a dose (2% wt/ vol in phosphate buffer saline) was injected intraperitoneally 3ml/kg. Then, they were anaesthetized and the brain was dissected out. Specimens from the brain were then processed for histological, immunohistochemical and electron microscopic examination. Results: The present study observed leakage of the Evan’s blue dye in group II. There was a highly significant increase in IgG and amyloid deposits. Faint localization of the tight junction protein occludin in the wall of small blood vessels was detected. Moreover, some neurons appeared with deeply stained pyknotic nuclei with areas of mononuclear cellular infiltration. By electron microscope, the tight junctions between the endothelial cells of the small blood vessels were not clearly seen in this group. Group III showed that caffeine was not associated with leakage of the Evan’s blue dye. Immunohistochemical and ultra structural examination revealed that caffeine preserved most of the histological profile of the hippocampus. Significant decrease in the number of IgG and amyloid deposits compared to group II was detected as well. Conclusion: The results of the current study revealed that administration of caffeine might protect against the disruption of blood brain barrier integrity encountered in this model of Alzheimer’s disease and therefore caffeine might help as a protective agent against this disease.