Abstract 13129: Ketogenic Diet Reduces Glucose Uptake and Infarct Volume in Murine Stroke
Ischemic penumbra, the hypoperfused but viable tissue at risk surrounding the irreversibly injured core, has been a target for neuroprotective and reperfusion therapies in stroke. Ketogenic diet (KD) is a high fat, low carbohydrate diet efficacious in refractory forms of epilepsy. KD is associated with high circulating levels of ketone bodies that serve as an efficient fuel in the brain. In this study, we investigated the effect of KD on cerebral glucose uptake and tissue outcome after ischemic stroke. Mice (male, C57BL/6J) received either KD (fat 84%, carbohydrate 0%, protein 16%) or control diet that was identical except for fat and carbohydrate contents (fat 16%, carbohydrate 65%, protein 19%, AIN-93G; TestDiet, IN) for 4 weeks starting at 6 weeks of age. Mice were then subjected to middle cerebral artery occlusion using an intraluminal filament (fMCAO) for 1h. In one cohort, dynamic 18F-fluodeoxyglucose (FDG) PET imaging was performed under isoflurane anesthesia starting 15 min after fMCAO and continued for 1h. The FDG net influx rate (Ki) was measured in ischemic core, penumbra and contralateral non-ischemic brain. In mice on control diet, we found increased glucose uptake in penumbra compared to ischemic core and both ipsilateral and contralateral non-ischemic tissue (n=6). Increased penumbral glucose uptake rate was significantly diminished in KD group compared to controls group (0.42±0.08 vs. 0.71±0.19, p<0.05). KD also significantly reduced glucose uptake rate in contralateral non-ischemic tissue but not in the core. In a separate cohort, we measured infarct volume 24 hours after 1h fMCAO in KD and control mice using 2,3,5-triphenyltetrazolium chloride staining. KD reduced infarct (indirect) volume by 36% (77±18 vs. 49±9 mm, p<0.05). These data suggest a role for KD in stroke prophylaxis, and implicate improved energy metabolism in ischemic penumbra as a mechanism.
- © 2012 by American Heart Association, Inc.