Different ketogenesis strategies lead to disparate seizure outcomes

Alison Dolce, Polan Santos, Weiran Chen, Ahmet Hoke, Adam L. Hartman

Research output: Contribution to journalArticle

Abstract

Background: Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration. Methods: Male NIH Swiss mice (aged 3–4 weeks) were fed for 12–13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 Hz threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondrial respiration was tested in brain tissue isolated from similarly-fed seizure-naïve mice. Results: KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondrial respiration between diet regimens. Interpretation: KD and CD-IF do not share identical antiseizure mechanisms. These differences were not explained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further.

Original languageEnglish (US)
Pages (from-to)90-97
Number of pages8
JournalEpilepsy Research
Volume143
DOIs
StatePublished - Jul 1 2018

Keywords

  • 6 Hz test
  • Beta-hydroxybutyrate
  • Kainic acid
  • Mitochondria

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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