Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats

• Published in: Frontiers in molecular neuroscience Vol. 12; p. 45
• Main Authors: Kovács, Zsolt, D'Agostino, Dominic P, Diamond, David M, Ari, Csilla
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 28.02.2019; Frontiers Media S.A
• Subjects: absence epilepsy; Adenosine; Albinism; Alzheimer's disease; Animal models; Body weight; Convulsions & seizures; Cyclooxygenase-1; Cyclooxygenase-2; Cytokines; Dietary supplements; Electrodes; Electroencephalography; Epilepsy; Food; Indomethacin; Inflammation; Injection; ketone supplements; Ketones; ketosis; Laboratories; Lipopolysaccharides; LPS; Neuroscience; Neurosciences; Rodents; Sleep and wakefulness; WAG/Rij rats; Hungary; United States > US; absence epilepsy; ketone supplements; WAG/Rij rats; ketosis; inflammation; LPS
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2019.00045

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 supplement-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 IP 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 IP LPS (50 μg/kg) (KEKS + LPS), as well as KEKS food with IP 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.