Abstract T P84: Beneficial Stroke Outcomes Following Epicatechin Consumption in Young and Older Mice

Abstract

Background: The consumption of flavanol containing foods, including (-)-epicatechin, has been linked to lower incidence of cardiovascular disease and stroke. We have previously demonstrated that epicatechin prophylaxis reduces stroke-induced anatomical and functional deficits in young, healthy mice; yet clinical stroke is primarily a disease of the elderly. Since neuroinflammation and vascular dysfunction are associated with aging, we aimed to test whether epicatechin is also protective in aging mice subjected to experimental stroke, and if so, whether this results from reduced glial cell activation and blood brain barrier permeability. Methods: Twelve-month-old wildtype and C57BL/6 Nrf2 knockout mice were administered 15mg/kg epicatechin, the minimum effective dose in young, healthy mice, prior to permanent distal middle cerebral artery occlusion. Mice were evaluated for functional recovery at one day post-stroke using the Adhesive Removal Test. Infarct volume, gliosis, and blood brain barrier permeability estimates were conducted seven days following stroke. Additionally, we compared anastomosis in wildtype and Nrf2 knockout mice and assessed hemorrhage frequency in studies using four- and 12-month-old mice. Results: Consistent with previous results in young mice, 12-month-old wildtype mice pretreated with epicatechin showed significant reductions in infarct volume and latency to remove adhesive tape relative to vehicle-treated controls, while Nrf2 knockout mice were not protected by epicatechin. Interestingly, epicatechin did not reduce Iba1 immunoreactivity or mouse IgG extravasation at seven days post-stroke. Similarly, there were no significant differences in anastomosis or spontaneous hemorrhage between wildtype and Nrf2 knockouts, indicating that cerebral vascular physiology is similar and gross vascular integrity was unaffected by treatment. Conclusion: Thus, although epicatechin prophylaxis reduces infarct volume and functional deficits, it does not exert sustained effects on gliosis or cerebrovascular integrity in aging mice.