Crocin protects against cerebral-ischemia-induced damage in aged rats through maintaining the integrity of blood-brain barrier

Background: A clear relationship exists between oxidative stress and disruption of blood-brain barrier (BBB) during cerebral ischemia, in which aging may exacerbate the extent of leakage. Here, we aim to examine the potential role of a water-soluble carotenoid-based antioxidant crocin on BBB damage in aged rats following cerebral ischemia. Methods: A two months oral administration of crocin was applied to 24-month-old rats followed by an induction of brain ischemia by middle cerebral artery occlusion (MCAO). Brain infarction volume, water content, and neurological behavior assessments were measured in these animals at 24 hours after MCAO as compared to vehicle-treated controls. Evans blue dye extravasation assay was used to evaluate the BBB integrity. The levels of tight junction proteins, oxidative stress, and MMP (matrix metalloproteinases) activities were also determined in the ipsilateral brains of the MCAO-treated rats. Results: MCAO-induced brain injury was alleviated by the pretreatment of crocin. Crocin-treated animals also showed the preserved BBB function in the presence of ischemic injury. The loss of tight junction proteins and enhanced NADPH oxidase in the ipsilateral brains of the MCAO-treated rats were both reduced by crocin. Finally, the induction of MMP-2 and MMP-9 by cerebral ischemia was partially blocked by crocin in aged rats. Conclusion: These findings indicate that crocin or related antioxidants may protect against cerebral ischemia of elderly patients by maintaining the integrity of BBB in aged rats, an effect likely through repressing the activation of matrix metalloproteinase pathway.