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.