Figure 2.

Seizure-like activity in an in vivo model is acutely blocked by decanoic acid (DA) and related compounds but not by ketones. The MCT ketogenic diet involves the oral intake of (A) medium-chain triglycerides, which are converted into the fatty acids decanoic acid and octanoic acid in the intestine. These medium-chain fatty acids are then transferred to the liver, where they are further metabolized to form ketone bodies. Fatty acids and ketones are transported in the blood to the brain where they are able to cross the blood brain barrier. Following the identification of decanoic acid as a potential therapeutic effector of the MCT ketogenic diet in Dictyostelium, its seizure control activity was compared to that of the ketones acetone and β-hydroxybutyrate (BHB), with seizure-like activity induced in a rat hippocampal slice model following (B) pentelentetrazol (PTZ) or (C) low magnesium treatment. In both models, epileptiform activity was not blocked by either ketones (BHB or acetone) at high concentrations (10 mM). In contrast, the medium-chain fatty acid, DA rapidly blocked activity at 1 mM. Data is derived from Chang et al. (2016). (D,E) A range of novel compounds and related structures implicated through the use of Dictyostelium have also been demonstrated to show seizure control activity, where seizure-like activity is induced in a rat hippocampal slice model following PTZ treatment. Data derived from Chang et al. (2014).