The behavioural and pathophysiological effects of the ketogenic diet on mild traumatic brain injury in adolescent rats

Sabrina Salberg; Himanthri Weerwardhena; Reid Collins; Raylene A Reimer; Richelle Mychasiuk

doi:10.1016/j.bbr.2019.112225

The behavioural and pathophysiological effects of the ketogenic diet on mild traumatic brain injury in adolescent rats

Behav Brain Res. 2019 Dec 30:376:112225. doi: 10.1016/j.bbr.2019.112225. Epub 2019 Sep 10.

Authors

Sabrina Salberg¹, Himanthri Weerwardhena², Reid Collins², Raylene A Reimer³, Richelle Mychasiuk⁴

Affiliations

¹ Department of Psychology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, The University of Calgary, Calgary, AB, Canada; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.
² Department of Psychology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, The University of Calgary, Calgary, AB, Canada.
³ Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
⁴ Department of Psychology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, The University of Calgary, Calgary, AB, Canada; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia. Electronic address: Richelle.mychasiuk@monash.edu.

PMID: 31518660
DOI: 10.1016/j.bbr.2019.112225

Abstract

Mild traumatic brain injury (mTBI), caused by an insult to the head, results in a cascade of molecular imbalance that includes altered glucose metabolism, mitochondrial dysfunction, and increases in reactive oxygen species. Although glucose is the primary energy source for the brain, it becomes an inefficient substrate following injury, and the brain is primed to use alternative substrates (such as ketones). The ketogenic diet (KD), a high-fat, low-carbohydrate diet, forces the brain to utilize ketones over glucose for energy. Given that mTBIs are commonly experienced during adolescence, our study sought to examine the effects of the KD on recovery from mTBI in adolescent rats. This was done via two experiments; the first of which animals were fed the KD prior to a mTBI in order to investigate the neuroprotective potential of the diet, and the second the animals were fed the KD following a mTBI to examine the therapeutic potential. Male and female Sprague Dawley rats were assigned to receive a control standard diet or the KD (either pre-injury or post-injury), then further randomized to receive a sham or mTBI. Animals were tested on 6 behavioural measures designed to examine post-concussive symptomology, and mRNA analysis of the brain and small intestine were performed. Pre-injury exposure to the KD offered some neuroprotection, reducing balance and motor impairments while increasing exploratory behaviour and telomere length. Consumption of the KD following the injury also provided some therapeutic benefit, reducing both anxiety- and depressive-like behaviours. The timing of KD administration also differentially modified expression of prefrontal cortex, hippocampus, and intestinal mRNA for our genes of interest (Fgf2, Iba1, Opa1, Sirt1, Claudin3, OCC, and ZO1) This study demonstrates the neuroprotective and therapeutic potential of the KD for mTBI and warrants further investigation.

Keywords: Concussion; Hippocampus; Neuroprotective; Prefrontal cortex; Small intestine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Behavior, Animal / physiology
Brain / physiopathology
Brain Concussion / diet therapy*
Brain Concussion / physiopathology
Diet, Ketogenic / methods*
Diet, Ketogenic / psychology*
Disease Models, Animal
Exploratory Behavior / physiology
Female
Hippocampus / physiopathology
Male
Prefrontal Cortex / physiopathology
Rats
Rats, Sprague-Dawley