Crocetin Attenuates Spatial Learning Dysfunction and Hippocampal Injury in a Model of Vascular Dementia

Chronic cerebral hypoperfusion produces brain ischemia and is associated with related memory impairment. In this study, we prepared crocetin from crocin (the main water soluble pigment in saffron stigmas) in an acidic hydrolysis and its purity was evaluated using spectrophotometry, thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The memory enhancing effect of crocetin was then studied in a rat model of chronic cerebral hypoperfusion. Different doses of crocetin were administered intraperitoneally (i.p.). The spatial learning and memory function were tested using Morris water maze, after permanent occlusion of common carotids. Finally, the animals were euthanatized in CO2 chamber and histopathological changes in cerebral cortex and hippocampus were investigated. The results indicated that the escape latency time significantly decreased in crocetin treated rats, in comparison with control animals. Also, the percentage of time spent and traveled distance in target quadrant on final test trial day increased in crocetin 8 mg/kg group, compared to control group, while no difference was observed between groups in swimming speed. All behavioral results were confirmed by histopathological analysis. According to our data, crocetin (8 mg/kg) could properly protect cerebrocortical and hippocampus neurons against ischemia. In conclusion, treatment with crocetin could effectively prevent neuropathological alterations in hippocampus thereby resulting in improvement of spatial learning memory in rats after chronic cerebral hypoperfusion.