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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00045

Exogenous ketone supplementation decreased the lipopolysaccharide-induced increase in absence epileptic activity in Wistar Albino Glaxo Rijswijk rats

  • 1Eötvös Loránd University, Hungary
  • 2University of South Florida, United States

It has been demonstrated previously that exogenous ketone supplements, such as ketone ester (KE) decreased absence epileptic activity in a well-studied animal model of human absence epilepsy, Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. It is known that lipopolysaccharide (LPS)-generated changes in inflammatory processes increase absence epileptic activity, while previous studies show that ketone supplements-evoked ketosis can modulate inflammatory processes. Thus, we investigated in the present study whether administration of exogenous ketone supplements, which were mixed with standard rodent chow (containing 10 % KE + 10 % ketone salt/KS, % by weight, KEKS) for 10 days can modulate the LPS-evoked changes in absence epileptic activity in WAG/Rij rats. At first, KEKS food alone was administered and changes in spike-wave discharge (SWD) number, SWD time, discharge frequency within SWDs, blood glucose and beta-hydroxybutyrate (βHB) levels, as well as body weight and sleep-waking stages were measured. In a separate experiment, intraperitoneal (i.p.) injection of LPS (50 µg/kg) alone and a cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitor indomethacin (10 mg/kg) alone, as well as combined i.p. injection of indomethacin with LPS (indomethacin + LPS) were applied in WAG/Rij rats to elucidate their influences on SWD number. In order to determine whether KEKS food can modify the LPS-evoked changes in SWD number, KEKS food in combination with i.p. LPS (50 µg/kg) (KEKS + LPS), as well as KEKS food with i.p. indomethacin (10 mg/kg) and LPS (50 µg/kg) (KEKS + indomethacin + LPS) were also administered. We demonstrated that KEKS food significantly increased blood βHB levels and decreased not only the spontaneously generated absence epileptic activity (SWD number), but also the LPS-evoked increase in SWD number in WAG/Rij rats. Our results suggest that administration of exogenous ketone supplements (ketogenic foods) may be a promising therapeutic tool in the treatment of epilepsy.

Keywords: ketone supplements, Ketosis, LPS (lipopolysaccharide), Inflammation, absence epilepsy, WAG/Rij rats

Received: 25 Nov 2018; Accepted: 05 Feb 2019.

Edited by:

MICHELE PAPA, Università degli Studi della Campania Luigi Vanvitelli Caserta, Italy

Reviewed by:

Masahito Kawamura, Jikei University School of Medicine, Japan
Giovanni Cirillo, Second University of Naples, Italy  

Copyright: © 2019 Kovacs, D'Agostino, Diamond and Ari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Csilla Ari, University of South Florida, Tampa, 33620, Florida, United States,