Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats
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 i...
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00045/full |
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| author | Zsolt Kovács Dominic P. D'Agostino Dominic P. D'Agostino David M. Diamond David M. Diamond Csilla Ari |
| author_facet | Zsolt Kovács Dominic P. D'Agostino Dominic P. D'Agostino David M. Diamond David M. Diamond Csilla Ari |
| author_sort | Zsolt Kovács |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T10:57:08Z |
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| id | doaj.art-0c35bcdd8abe4d2c902da4925b3ebcc8 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-21T10:57:08Z |
| publishDate | 2019-02-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-0c35bcdd8abe4d2c902da4925b3ebcc82022-12-21T19:06:28ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-02-011210.3389/fnmol.2019.00045438813Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk RatsZsolt Kovács0Dominic P. D'Agostino1Dominic P. D'Agostino2David M. Diamond3David M. Diamond4Csilla Ari5Department of Biology, ELTE Eötvös Loránd University, Savaria University Centre, Szombathely, HungaryLaboratory of Metabolic Medicine, Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesInstitute for Human and Machine Cognition, Ocala, FL, United StatesLaboratory of Metabolic Medicine, Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesComparative Neuroscience Research Laboratory, Department of Psychology, University of South Florida, Tampa, FL, United StatesComparative Neuroscience Research Laboratory, Department of Psychology, University of South Florida, Tampa, FL, United StatesIt 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.https://www.frontiersin.org/article/10.3389/fnmol.2019.00045/fullketone supplementsketosisLPSinflammationabsence epilepsyWAG/Rij rats |
| spellingShingle | Zsolt Kovács Dominic P. D'Agostino Dominic P. D'Agostino David M. Diamond David M. Diamond Csilla Ari Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats Frontiers in Molecular Neuroscience ketone supplements ketosis LPS inflammation absence epilepsy WAG/Rij rats |
| title | Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats |
| title_full | Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats |
| title_fullStr | Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats |
| title_full_unstemmed | Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats |
| title_short | Exogenous Ketone Supplementation Decreased the Lipopolysaccharide-Induced Increase in Absence Epileptic Activity in Wistar Albino Glaxo Rijswijk Rats |
| title_sort | exogenous ketone supplementation decreased the lipopolysaccharide induced increase in absence epileptic activity in wistar albino glaxo rijswijk rats |
| topic | ketone supplements ketosis LPS inflammation absence epilepsy WAG/Rij rats |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00045/full |
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