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

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.

journal_name

Behav Brain Res

authors

Salberg S,Weerwardhena H,Collins R,Reimer RA,Mychasiuk R

doi

10.1016/j.bbr.2019.112225

subject

Has Abstract

pub_date

2019-12-30 00:00:00

pages

112225

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(19)30869-1

journal_volume

376

pub_type

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