Ketogenic Diet as a potential treatment for traumatic brain injury in mice

• Published in: Scientific reports Vol. 11; no. 1; p. 23559
• Main Authors: Har-Even, Meirav, Rubovitch, Vardit, Ratliff, Whitney A., Richmond-Hacham, Bar, Citron, Bruce A., Pick, Chaim G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 692/617; Animals; Anxiety; Astrocytes - pathology; Brain Injuries, Traumatic - blood; Brain Injuries, Traumatic - diet therapy; Brain Injuries, Traumatic - psychology; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cognitive ability; Cognitive Dysfunction - diet therapy; Cognitive Dysfunction - psychology; Dentate gyrus; Diet; Diet, Ketogenic; Disease Models, Animal; Head injuries; Head Injuries, Closed - blood; Head Injuries, Closed - diet therapy; Head Injuries, Closed - psychology; High fat diet; Hippocampus - metabolism; Hippocampus - pathology; Humanities and Social Sciences; Ketogenesis; Ketone Bodies - blood; Ketones; Low carbohydrate diet; Male; Maze Learning; Mice; Mice, Inbred ICR; multidisciplinary; Neurodegeneration; Neurons - pathology; Neuroprotection; Pattern recognition; Recognition, Psychology; Science; Science (multidisciplinary); SIRT1 protein; Sirtuin 1 - metabolism; Temporal lobe; Traumatic brain injury
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-02849-0

Traumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed ketogenic diet (KD) perform better in learning tasks than those fed standard diet (SD) following brain injury. The goal of this study was to examine whether KD is a neuroprotective in TBI mouse model. We utilized a closed head injury model to induce TBI in mice, followed by up to 30 days of KD/SD. Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y-maze and Novel Object Recognition tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating TBI.