Effects of ketogenic diet and caloric restriction on ischemic tolerance

The ketogenic diet (KD) is used to treat a number of brain pathologies. In this study, we undertook detailed transcriptomic profiling of rat brain after KD and ischemic stroke to uncover effects of KD and its specific mechanisms. We evaluated how a 2-month KD affected gene expression in intact brain tissue and after middle cerebral artery occlusion (MCAO). We found transcriptional reprogramming in the brain after stroke and KD treatment. KD altered the expression of genes involved in the regulation of glucose and fatty acid metabolism, mitochondrial function, immune response, Wnt-associated signaling, stem cell development, and neurotransmission in both intact rats and after MCAO. The experiments were performed on young (3 months, 320–350 g) male Wistar rats. The rats were divided into 2 experimental groups: rats fed a standard diet (3227 kcal/kg, of which fats 367 kcal/kg (11%), proteins 768 kcal/kg (24%), carbohydrates 2091 kcal/kg (65%); N1324 Altromin, Germany) and rats fed ketognic diet with a high fat and low carbohydrate content (6431 kcal/kg, of which fats 5405 kcal/kg (84%), proteins 680 kcal/kg (11%), carbohydrates 346 kcal/kg (5%); C 1084, Altromin, Germany). The rats were fed the selected diet for 2 months. Thereafter, the group of rats was subjected to middle cerebral artery occlusion (MCAO), and all rats were then fed the same diet for further 2 weeks.