No abstract

The ketogenic diet (KD), or the low‐carbohydrate and high‐fat diet, has served as a therapeutic for medically intractable epilepsy for the past ninety years. Recent studies have shown the neurological benefits derived from ketone bodies. However, KD's impact on overall in vivo brain function remains largely unexplored. The aim of this study was to characterize the interaction between specialized nutrition and in vivo brain function. Subjects were age‐matched and gender‐matched young wild type mice models, divided into two groups based on diet: Western (control) diet or KD. We employed multimodal, non‐invasive neuroimaging (MRI/MRS) to determine in vivo brain cerebral blood flow and energy metabolites. We also assessed the animal's memory and learning ability with the Radial Arm Water Maze and the Novel Object Recognition Test. In addition, we performed western blots and BBB function analysis. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between Western and Ketogenic diet – the KD group exhibited significantly higher cerebral blood flow in the dorsal thalamus and the hypothalamus compared to the control. We observed significant modulation of the metabolites alanine and lactate, and identified a potential interaction with astrocytes. When examining the behavioral test results, there is indication that KD fortifies various memory and sensory functions, consist with our CBF data. Furthermore, KD mice exhibited significantly higher brain endothelial NOS and brain capillary P‐glycoprotein, as well as a significantly lower expression of the mechanistic target of Rapamycin. Our novel findings demonstrate KD produces noticeable shifts in brain vascular and metabolic function, while maintaining cognition in a young mice model. These results provide rationale for KD as a viable early interventional dietary measure.Support or Funding InformationThis research was supported by NIH grant K01AG040164.