Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet
-
Azam Ildarabadi
Abstract
Childhood epilepsy affects up to 1 % of children. It has been shown that 30 % of patients are resistant to drug treatments, making further investigation of other potential treatment strategies necessary. One such approach is the ketogenic diet (KD) showing promising results and potential benefits beyond the use of current antiepileptic drugs. This study aims to investigate the effects of KD on inflammation and oxidative stress, as one of the main suggested mechanisms of neuroprotection, in children with epilepsy. This narrative review was conducted using the Medline and Google Scholar databases, and by searching epilepsy, drug-resistant epilepsy, child, children, ketogenic, ketogenic diet, diet, ketogenic, keto, ketone bodies (BHB), PUFA, gut microbiota, inflammation, inflammation mediators, neurogenic inflammation, neuroinflammation, inflammatory marker, adenosine modulation, mitochondrial function, MTOR pathway, Nrf2 pathway, mitochondrial dysfunction, PPARɣ, oxidative stress, ROS/RNS, and stress oxidative as keywords. Compelling evidence underscores inflammation and oxidative stress as pivotal factors in epilepsy, even in cases with genetic origins. The ketogenic diet effectively addresses these factors by reducing ROS and RNS, enhancing antioxidant defenses, improving mitochondrial function, and regulating inflammatory genes. Additionally, KD curbs pro-inflammatory cytokine and chemokine production by dampening NF-κB activation, inhibiting the NLRP3 inflammasome, increasing brain adenosine levels, mTOR pathway inhibition, upregulating PPARɣ expression, and promoting a healthy gut microbiota while emphasizing the consumption of healthy fats. KD could be considered a promising therapeutic intervention in patients with epilepsy particularly in drug-resistant epilepsy cases, due to its targeted approach addressing oxidative stress and inflammatory mechanisms.
Acknowledgment
We would like to thank Dr. Noosha Samieefar for her invaluable comments on our manuscript.
-
Research ethics: Not applicable.
-
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: Not applicable.
References
Al Bander, Z., Nitert, M.D., Mousa, A., and Naderpoor, N. (2020). The gut microbiota and inflammation: an overview. Int. J. Environ. Res. Public Health 17: 7618, https://doi.org/10.3390/ijerph17207618.Suche in Google Scholar PubMed PubMed Central
Aronica, E., Fluiter, K., Iyer, A., Zurolo, E., Vreijling, J., Van Vliet, E., Baayen, J., and Gorter, J. (2010). Expression pattern of miR‐146a, an inflammation‐associated microRNA, in experimental and human temporal lobe epilepsy. Eur. J. Neurosci. 31: 1100–1107, https://doi.org/10.1111/j.1460-9568.2010.07122.x.Suche in Google Scholar PubMed
Attaye, I., van Oppenraaij, S., Warmbrunn, M.V., and Nieuwdorp, M. (2021). The role of the gut microbiota on the beneficial effects of ketogenic diets. Nutrients 14: 191, https://doi.org/10.3390/nu14010191.Suche in Google Scholar PubMed PubMed Central
Balosso, S., Ravizza, T., Perego, C., Peschon, J., Campbell, I.L., De Simoni, M.G., and Vezzani, A. (2005). Tumor necrosis factor‐α inhibits seizures in mice via p75 receptors. Ann Neurol 57: 804–812, https://doi.org/10.1002/ana.20480.Suche in Google Scholar PubMed
Barone, F., Arvin, B., White, R., Miller, A., Webb, C., Willette, R., Lysko, P., and Feuerstein, G. (1997). Tumor necrosis factor-α: a mediator of focal ischemic brain injury. Stroke 28: 1233–1244, https://doi.org/10.1161/01.str.28.6.1233.Suche in Google Scholar PubMed
Beam, A., Clinger, E., and Hao, L. (2021). Effect of diet and dietary components on the composition of the gut microbiota. Nutrients 13: 2795, https://doi.org/10.3390/nu13082795.Suche in Google Scholar PubMed PubMed Central
Beattie, E.C., Stellwagen, D., Morishita, W., Bresnahan, J.C., Ha, B.K., Von Zastrow, M., Beattie, M.S., and Malenka, R.C. (2002). Control of synaptic strength by glial TNFα. Science 295: 2282–2285, https://doi.org/10.1126/science.1067859.Suche in Google Scholar PubMed
Beghi, E. (2020). The epidemiology of epilepsy. Neuroepidemiology 54: 185–191, https://doi.org/10.1159/000503831.Suche in Google Scholar PubMed
Ben-Menachem, E., Kyllerman, M., and Marklund, S. (2000). Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies. Epilepsy Res 40: 33–39, https://doi.org/10.1016/s0920-1211(00)00096-6.Suche in Google Scholar PubMed
Bezzi, P., Domercq, M., Brambilla, L., Galli, R., Schols, D., De Clercq, E., Vescovi, A., Bagetta, G., Kollias, G., Meldolesi, J., et al.. (2001). CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity. Nat. Neurosci. 4: 702–710, https://doi.org/10.1038/89490.Suche in Google Scholar PubMed
Bianchi, M.E. and Agresti, A. (2005). HMG proteins: dynamic players in gene regulation and differentiation. Curr. Opin. Genet. Dev. 15: 496–506, https://doi.org/10.1016/j.gde.2005.08.007.Suche in Google Scholar PubMed
Bonanno, G., Raiteri, L., Milanese, M., Zappettini, S., Melloni, E., Pedrazzi, M., Passalacqua, M., Tacchetti, C., Usai, C., and Sparatore, B. (2007). The high‐mobility group box 1 cytokine induces transporter‐mediated release of glutamate from glial subcellular particles (gliosomes) prepared from in situ‐matured astrocytes. Int. Rev. Neurobiol. 82: 73–93, https://doi.org/10.1016/S0074-7742(07)82004-6.Suche in Google Scholar PubMed
Cacheaux, L.P., Ivens, S., David, Y., Lakhter, A.J., Bar-Klein, G., Shapira, M., Heinemann, U., Friedman, A., and Kaufer, D. (2009). Transcriptome profiling reveals TGF-β signaling involvement in epileptogenesis. J. Neurosci. 29: 8927–8935, https://doi.org/10.1523/jneurosci.0430-09.2009.Suche in Google Scholar
Cardenas-Rodriguez, N., Huerta-Gertrudis, B., Rivera-Espinosa, L., Montesinos-Correa, H., Bandala, C., Carmona-Aparicio, L., and Coballase-Urrutia, E. (2013). Role of oxidative stress in refractory epilepsy: evidence in patients and experimental models. Int. J. Mol. Sci. 14: 1455–1476, https://doi.org/10.3390/ijms14011455.Suche in Google Scholar PubMed PubMed Central
Celona, B., Weiner, A., Di Felice, F., Mancuso, F.M., Cesarini, E., Rossi, R.L., Gregory, L., Baban, D., Rossetti, G., Grianti, P., et al.. (2011). Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output. PLoS Biol. 9: e1001086, https://doi.org/10.1371/journal.pbio.1001086.Suche in Google Scholar PubMed PubMed Central
Chen, C. and Bazan, N.G. (2005). Endogenous PGE2 regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 93: 929–941, https://doi.org/10.1152/jn.00696.2004.Suche in Google Scholar PubMed
Chriett, S., Dąbek, A., Wojtala, M., Vidal, H., Balcerczyk, A., and Pirola, L. (2019). Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. Sci. Rep. 9: 742, https://doi.org/10.1038/s41598-018-36941-9.Suche in Google Scholar PubMed PubMed Central
Chung, J.-I., Kim, A.Y., Lee, S.H., and Baik, E.J. (2013). Seizure susceptibility in immature brain due to lack of COX-2-induced PGF2α. Exp. Neurol. 249: 95–103, https://doi.org/10.1016/j.expneurol.2013.08.014.Suche in Google Scholar PubMed
Chyra, M., Świętochowska, E., Górska-Flak, K., Dudzińska, M., and Oświęcimska, J. (2021). The effect of the ketogenic diet on leptin, chemerin and resistin levels in children with epilepsy. Neuro Endocrinol. Lett. 42: 489–499.Suche in Google Scholar
Cunnane, S.C. (2004). Metabolism of polyunsaturated fatty acids and ketogenesis: an emerging connection. Prostaglandins Leukot. Essent. Fatty Acids 70: 237–241, https://doi.org/10.1016/j.plefa.2003.11.002.Suche in Google Scholar PubMed
Dahlin, M., Singleton, S.S., David, J.A., Basuchoudhary, A., Wickström, R., Mazumder, R., and Prast-Nielsen, S. (2022). Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet. EBioMedicine 80: 104061, https://doi.org/10.1016/j.ebiom.2022.104061.Suche in Google Scholar PubMed PubMed Central
De Simoni, M.G., Perego, C., Ravizza, T., Moneta, D., Conti, M., Marchesi, F., De Luigi, A., Garattini, S., and Vezzani, A. (2000). Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur. J. Neurosci. 12: 2623–2633, https://doi.org/10.1046/j.1460-9568.2000.00140.x.Suche in Google Scholar PubMed
De Toma, I., Rossetti, G., Zambrano, S., Bianchi, M.E., and Agresti, A. (2014). Nucleosome loss facilitates the chemotactic response of macrophages. J. Intern. Med. 276: 454–469, https://doi.org/10.1111/joim.12286.Suche in Google Scholar PubMed
Dhillon, K.K., and Gupta, S. (2023). Biochemistry, ketogenesis. In: StatPearls. Treasure Island (FL): StatPearls Publishing, Copyright © 2023, StatPearls Publishing LLC.Suche in Google Scholar
Dilena, R., Mauri, E., Aronica, E., Bernasconi, P., Bana, C., Cappelletti, C., Carrabba, G., Ferrero, S., Giorda, R., Guez, S., et al.. (2019). Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection–related epilepsy syndrome. Epilepsia Open 4: 344–350, https://doi.org/10.1002/epi4.12317.Suche in Google Scholar PubMed PubMed Central
Dupuis, N., Curatolo, N., Benoist, J.F., and Auvin, S. (2015). Ketogenic diet exhibits anti-inflammatory properties. Epilepsia 56: e95–e98, https://doi.org/10.1111/epi.13038.Suche in Google Scholar PubMed
El-Rashidy, O.F., Youssef, M.M., Elgendy, Y.G., Mohsen, M.A., Morsy, S.M., Dawh, S.A., and Saad, K. (2020). Selenium and antioxidant levels in children with intractable epilepsy receiving ketogenic diet. Acta Neurol. Belg. 120: 375–380, https://doi.org/10.1007/s13760-020-01310-9.Suche in Google Scholar PubMed
Fellin, T., Gomez-Gonzalo, M., Gobbo, S., Carmignoto, G., and Haydon, P.G. (2006). Astrocytic glutamate is not necessary for the generation of epileptiform neuronal activity in hippocampal slices. J. Neurosci. 26: 9312–9322, https://doi.org/10.1523/jneurosci.2836-06.2006.Suche in Google Scholar PubMed PubMed Central
Friedman, A. and Dingledine, R. (2011). Molecular cascades that mediate the influence of inflammation on epilepsy. Epilepsia 52: 33–39, https://doi.org/10.1111/j.1528-1167.2011.03034.x.Suche in Google Scholar PubMed PubMed Central
Friedman, A., Kaufer, D., and Heinemann, U. (2009). Blood–brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy. Epilepsy Res 85: 142–149, https://doi.org/10.1016/j.eplepsyres.2009.03.005.Suche in Google Scholar PubMed PubMed Central
Galasso, J.M., Wang, P., Martin, D., and Silverstein, F.S. (2000). Inhibition of TNF-α can attenuate or exacerbate excitotoxic injury in neonatal rat brain. Neuroreport 11: 231–236, https://doi.org/10.1097/00001756-200002070-00002.Suche in Google Scholar PubMed
Gano, L.B., Patel, M., and Rho, J.M. (2014). Ketogenic diets, mitochondria, and neurological diseases. J. Lipid Res. 55: 2211–2228, https://doi.org/10.1194/jlr.r048975.Suche in Google Scholar PubMed PubMed Central
García-Rodríguez, D. and Giménez-Cassina, A. (2021). Ketone bodies in the brain beyond fuel metabolism: from excitability to gene expression and cell signaling. Front. Mol. Neurosci. 14: 732120, https://doi.org/10.3389/fnmol.2021.732120.Suche in Google Scholar PubMed PubMed Central
Gary, D.S., Bruce-Keller, A.J., Kindy, M.S., and Mattson, M.P. (1998). Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. J. Cereb. Blood Flow Metab. 18: 1283–1287, https://doi.org/10.1097/00004647-199812000-00001.Suche in Google Scholar PubMed
Greco, T., Glenn, T.C., Hovda, D.A., and Prins, M.L. (2016). Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity. J Cereb Blood Flow Metab 36: 1603–1613, https://doi.org/10.1177/0271678x15610584.Suche in Google Scholar
Grewal, G.K., Kukal, S., Kanojia, N., Saso, L., Kukreti, S., and Kukreti, R. (2017). Effect of oxidative stress on ABC transporters: contribution to epilepsy pharmacoresistance. Molecules 22: 365, https://doi.org/10.3390/molecules22030365.Suche in Google Scholar PubMed PubMed Central
Guo, Y., Wang, X., Jia, P., You, Y., Cheng, Y., Deng, H., Luo, S., and Huang, B. (2020). Ketogenic diet aggravates hypertension via NF-κB-mediated endothelial dysfunction in spontaneously hypertensive rats. Life Sci. 258: 118124, https://doi.org/10.1016/j.lfs.2020.118124.Suche in Google Scholar PubMed
Hallböök, T., Sjölander, A., Åmark, P., Miranda, M., Bjurulf, B., and Dahlin, M. (2015). Effectiveness of the ketogenic diet used to treat resistant childhood epilepsy in Scandinavia. Eur. J. Paediatr. Neurol. 19: 29–36, https://doi.org/10.1016/j.ejpn.2014.09.005.Suche in Google Scholar PubMed
Hallenbeck, J.M. (2002). The many faces of tumor necrosis factor in stroke. Nat. Med. 8: 1363–1368, https://doi.org/10.1038/nm1202-1363.Suche in Google Scholar PubMed
Hasan-Olive, M.M., Lauritzen, K.H., Ali, M., Rasmussen, L.J., Storm-Mathisen, J., and Bergersen, L.H. (2019). A ketogenic diet improves mitochondrial biogenesis and bioenergetics via the PGC1α-SIRT3-UCP2 Axis. Neurochem. Res. 44: 22–37, https://doi.org/10.1007/s11064-018-2588-6.Suche in Google Scholar PubMed
Holtman, L., van Vliet, E.A., Edelbroek, P.M., Aronica, E., and Gorter, J.A. (2010). Cox-2 inhibition can lead to adverse effects in a rat model for temporal lobe epilepsy. Epilepsy Res 91: 49–56, https://doi.org/10.1016/j.eplepsyres.2010.06.011.Suche in Google Scholar PubMed
Hu, S., Sheng, W.S., Ehrlich, L.C., Peterson, P.K., and Chao, C.C. (2000). Cytokine effects on glutamate uptake by human astrocytes. Neuroimmunomodulation 7: 153–159, https://doi.org/10.1159/000026433.Suche in Google Scholar PubMed
Ivens, S., Kaufer, D., Flores, L.P., Bechmann, I., Zumsteg, D., Tomkins, O., Seiffert, E., Heinemann, U., and Friedman, A. (2007). TGF-β receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain 130: 535–547, https://doi.org/10.1093/brain/awl317.Suche in Google Scholar PubMed
Janigro, D., Nehlig, A., and Marchi, N. (2021). Inflammation and epilepsy. Springer, New Vistas.10.1007/978-3-030-67403-8Suche in Google Scholar
Jeong, E.A., Jeon, B.T., Shin, H.J., Kim, N., Lee, D.H., Kim, H.J., Kang, S.S., Cho, G.J., Choi, W.S., and Roh, G.S. (2011). Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Exp. Neurol. 232: 195–202, https://doi.org/10.1016/j.expneurol.2011.09.001.Suche in Google Scholar PubMed
Jiang, J., Ganesh, T., Du, Y., Quan, Y., Serrano, G., Qui, M., Speigel, I., Rojas, A., Lelutiu, N., and Dingledine, R. (2012). Small molecule antagonist reveals seizure-induced mediation of neuronal injury by prostaglandin E2 receptor subtype EP2. Proc. Natl. Acad. Sci. U.S.A. 109: 3149–3154, https://doi.org/10.1073/pnas.1120195109.Suche in Google Scholar PubMed PubMed Central
Jiang, J., Quan, Y., Ganesh, T., Pouliot, W.A., Dudek, F.E., and Dingledine, R. (2013). Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proc. Natl. Acad. Sci. U.S.A. 110: 3591–3596, https://doi.org/10.1073/pnas.1218498110.Suche in Google Scholar PubMed PubMed Central
Jiang, Z., Yin, X., Wang, M., Chen, T., Wang, Y., Gao, Z., and Wang, Z. (2022). Effects of ketogenic diet on neuroinflammation in neurodegenerative diseases. Aging Dis. 13: 1146–1165, https://doi.org/10.14336/ad.2021.1217.Suche in Google Scholar
Kaushik, M.K., Aritake, K., Kamauchi, S., Hayaishi, O., Huang, Z.-L., Lazarus, M., and Urade, Y. (2014). Prostaglandin D2 is crucial for seizure suppression and postictal sleep. Exp. Neurol. 253: 82–90, https://doi.org/10.1016/j.expneurol.2013.12.002.Suche in Google Scholar PubMed
Knowles, S., Budney, S., Deodhar, M., Matthews, S.A., Simeone, K.A., and Simeone, T.A. (2018). Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARγ2. Epilepsy Res 147: 71–74, https://doi.org/10.1016/j.eplepsyres.2018.09.009.Suche in Google Scholar PubMed PubMed Central
Koh, S., Dupuis, N., and Auvin, S. (2020). Ketogenic diet and neuroinflammation. Epilepsy Res 167: 106454, https://doi.org/10.1016/j.eplepsyres.2020.106454.Suche in Google Scholar PubMed
Kozyrskyj, A.L. and Prasad, A.N. (2004). The burden of seizures in Manitoba children: a population-based study. Can. J. Neurol. Sci. 31: 48–52, https://doi.org/10.1017/s0317167100002821.Suche in Google Scholar PubMed
Lehtimäki, K., Peltola, J., Koskikallio, E., Keränen, T., and Honkaniemi, J. (2003). Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures. Mol. Brain Res. 110: 253–260, https://doi.org/10.1016/s0169-328x(02)00654-x.Suche in Google Scholar PubMed
Levy, N., Milikovsky, D.Z., Baranauskas, G., Vinogradov, E., David, Y., Ketzef, M., Abutbul, S., Weissberg, I., Kamintsky, L., Fleidervish, I., et al.. (2015). Differential TGF-β signaling in glial subsets underlies IL-6–mediated epileptogenesis in mice. J. Immunol. 195: 1713–1722, https://doi.org/10.4049/jimmunol.1401446.Suche in Google Scholar PubMed
Li, G., Bauer, S., Nowak, M., Norwood, B., Tackenberg, B., Rosenow, F., Knake, S., Oertel, W.H., and Hamer, H.M. (2011). Cytokines and epilepsy. Seizure 20: 249–256, https://doi.org/10.1016/j.seizure.2010.12.005.Suche in Google Scholar PubMed
Li, S., Yan, T., Yang, J.-Q., Oberley, T.D., and Oberley, L.W. (2000). The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. Cancer Res. 60: 3927–3939.Suche in Google Scholar
Lu, B., Wang, H., Andersson, U., and Tracey, K.J. (2013). Regulation of HMGB1 release by inflammasomes. Protein Cell 4: 163–167, https://doi.org/10.1007/s13238-012-2118-2.Suche in Google Scholar PubMed PubMed Central
Lu, Y., Yang, Y.Y., Zhou, M.W., Liu, N., Xing, H.Y., Liu, X.X., and Li, F. (2018). Ketogenic diet attenuates oxidative stress and inflammation after spinal cord injury by activating Nrf2 and suppressing the NF-κB signaling pathways. Neurosci. Lett. 683: 13–18, https://doi.org/10.1016/j.neulet.2018.06.016.Suche in Google Scholar PubMed
MacEwan, D.J. (2002). TNF ligands and receptors–a matter of life and death. Br. J. Pharmacol. 135: 855, https://doi.org/10.1038/sj.bjp.0704549.Suche in Google Scholar PubMed PubMed Central
Maciejewska-Skrendo, A., Massidda, M., Tocco, F., and Leźnicka, K. (2022). The influence of the differentiation of genes encoding peroxisome proliferator-activated receptors and their coactivators on nutrient and energy metabolism. Nutrients 14: 5378, https://doi.org/10.3390/nu14245378.Suche in Google Scholar PubMed PubMed Central
Marcheselli, V.L. and Bazan, N.G. (1996). Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus: inhibition by a platelet-activating factor antagonist. J. Biol. Chem. 271: 24794–24799, https://doi.org/10.1074/jbc.271.40.24794.Suche in Google Scholar PubMed
Masino, S.A., Kawamura, M., Wasser, C.D., Pomeroy, L.T., and Ruskin, D.N. (2009). Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity. Curr. Neuropharmacol. 7: 257–268, https://doi.org/10.2174/157015909789152164.Suche in Google Scholar PubMed PubMed Central
McDaniel, S.S., Rensing, N.R., Thio, L.L., Yamada, K.A., and Wong, M. (2011). The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 52: e7–e11, https://doi.org/10.1111/j.1528-1167.2011.02981.x.Suche in Google Scholar PubMed PubMed Central
Meini, A., Benocci, A., Frosini, M., Sgaragli, G., Pessina, G., Aldinucci, C., Youmbi, G.T., and Palmi, M. (2000). Nitric oxide modulation of interleukin-1β-evoked intracellular Ca2+ release in human astrocytoma U-373 MG cells and brain striatal slices. J. Neurosci. 20: 8980–8986, https://doi.org/10.1523/jneurosci.20-24-08980.2000.Suche in Google Scholar PubMed PubMed Central
Milder, J. and Patel, M. (2012). Modulation of oxidative stress and mitochondrial function by the ketogenic diet. Epilepsy Res 100: 295–303, https://doi.org/10.1016/j.eplepsyres.2011.09.021.Suche in Google Scholar PubMed PubMed Central
Miller, L.G., Galpern, W.R., Dunlap, K., Dinarello, C.A., and Turner, T.J. (1991). Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain. Mol. Pharmacol. 39: 105–108.Suche in Google Scholar
Min, K.-j., Jou, I., and Joe, E. (2003). Plasminogen-induced IL-1β and TNF-α production in microglia is regulated by reactive oxygen species. Biochem. Biophys. Res. Commun. 312: 969–974, https://doi.org/10.1016/j.bbrc.2003.11.010.Suche in Google Scholar PubMed
Mirmohammadali, S.N. and Rosenkranz, S.K. (2023). Dietary phytochemicals, gut microbiota composition, and health outcomes in human and animal models. Biosci Microbiota Food Health 42: 152–171, https://doi.org/10.12938/bmfh.2022-078.Suche in Google Scholar PubMed PubMed Central
Moldofsky, H., Lue, F., Eisen, J., Keystone, E., and Gorczynski, R. (1986). The relationship of interleukin-1 and immune functions to sleep in humans. Psychosom. Med. 48: 309–318, https://doi.org/10.1097/00006842-198605000-00001.Suche in Google Scholar PubMed
Monda, V., Polito, R., Lovino, A., Finaldi, A., Valenzano, A., Nigro, E., Corso, G., Sessa, F., Asmundo, A., Di Nunno, N., et al.. (2020). Short-term physiological effects of a very low-calorie ketogenic diet: effects on adiponectin levels and inflammatory states. Int. J. Mol. Sci. 21: 3228, https://doi.org/10.3390/ijms21093228.Suche in Google Scholar PubMed PubMed Central
Murphy, C.C., Trevathan, E., and Yeargin‐Allsopp, M. (1995). Prevalence of epilepsy and epileptic seizures in 10‐year‐old children: results from the Metropolitan Atlanta Developmental Disabilities Study. Epilepsia 36: 866–872, https://doi.org/10.1111/j.1528-1157.1995.tb01629.x.Suche in Google Scholar PubMed
Napolitano, A., Longo, D., Lucignani, M., Pasquini, L., Rossi-Espagnet, M.C., Lucignani, G., Maiorana, A., Elia, D., De Liso, P., Dionisi-Vici, C., et al.. (2020). The ketogenic diet increases in vivo glutathione levels in patients with epilepsy. Metabolites 10: 504, https://doi.org/10.3390/metabo10120504.Suche in Google Scholar PubMed PubMed Central
Neal, E.G., Chaffe, H., Schwartz, R.H., Lawson, M.S., Edwards, N., Fitzsimmons, G., Whitney, A., and Cross, J.H. (2008). The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 7: 500–506, https://doi.org/10.1016/s1474-4422(08)70092-9.Suche in Google Scholar PubMed
Ni, F.-F., Li, C.-R., Liao, J.-X., Wang, G.-B., Lin, S.-F., Xia, Y., and Wen, J.-L. (2016). The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy. Seizure 38: 17–22, https://doi.org/10.1016/j.seizure.2016.03.006.Suche in Google Scholar PubMed
O’Banion, M.K., Miller, J.C., Chang, J.W., Kaplan, M.D., and Coleman, P.D. (1996). Interleukin‐1β induces prostaglandin G/H synthase‐2 (cyclooxygenase‐2) in primary murine astrocyte cultures. J. Neurochem. 66: 2532–2540, https://doi.org/10.1046/j.1471-4159.1996.66062532.x.Suche in Google Scholar PubMed
Oliveira, M., Furian, A., Rambo, L., Ribeiro, L., Royes, L., Ferreira, J., Calixto, J., and Mello, C. (2008). Modulation of pentylenetetrazol-induced seizures by prostaglandin E2 receptors. Neuroscience 152: 1110–1118, https://doi.org/10.1016/j.neuroscience.2008.01.005.Suche in Google Scholar PubMed
Patel, M. (2018). A metabolic paradigm for epilepsy. Epilepsy Curr. 18: 318–322, https://doi.org/10.5698/1535-7597.18.5.318.Suche in Google Scholar PubMed PubMed Central
Pauletti, A., Terrone, G., Shekh-Ahmad, T., Salamone, A., Ravizza, T., Rizzi, M., Pastore, A., Pascente, R., Liang, L.-P., Villa, B.R., et al. (2017). Targeting oxidative stress improves disease outcomes in a rat model of acquired epilepsy. Brain 140: 1885–1899, https://doi.org/10.1093/brain/awz130.Suche in Google Scholar PubMed PubMed Central
Pearson-Smith, J.N. and Patel, M. (2017). Metabolic dysfunction and oxidative stress in epilepsy. Int. J. Mol. Sci. 18: 2365, https://doi.org/10.3390/ijms18112365.Suche in Google Scholar PubMed PubMed Central
Pedrazzi, M., Raiteri, L., Bonanno, G., Patrone, M., Ledda, S., Passalacqua, M., Milanese, M., Melloni, E., Raiteri, M., Pontremoli, S., et al.. (2006). Stimulation of excitatory amino acid release from adult mouse brain glia subcellular particles by high mobility group box 1 protein. J. Neurochem. 99: 827–838, https://doi.org/10.1111/j.1471-4159.2006.04120.x.Suche in Google Scholar PubMed
Perillan, P.R., Chen, M., Potts, E.A., and Simard, J.M. (2002). Transforming growth factor-β1 regulates Kir2. 3 inward rectifier K+ channels via phospholipase C and protein kinase C-δ in reactive astrocytes from adult rat brain. J. Biol. Chem. 277: 1974–1980, https://doi.org/10.1074/jbc.m107984200.Suche in Google Scholar
Pinto, A., Bonucci, A., Maggi, E., Corsi, M., and Businaro, R. (2018). Anti-oxidant and anti-inflammatory activity of ketogenic diet: new perspectives for neuroprotection in Alzheimer’s disease. Antioxidants 7: 63, https://doi.org/10.3390/antiox7050063.Suche in Google Scholar PubMed PubMed Central
Polito, R., La Torre, M.E., Moscatelli, F., Cibelli, G., Valenzano, A., Panaro, M.A., Monda, M., Messina, A., Monda, V., Pisanelli, D., et al. (2023). The ketogenic diet and neuroinflammation: the action of beta-hydroxybutyrate in a microglial cell line. Int. J. Mol. Sci. 24: 3102, https://doi.org/10.3390/ijms24043102.Suche in Google Scholar PubMed PubMed Central
Poorshiri, B., Barzegar, M., Afghan, M., Shiva, S., Shahabi, P., Golchinfar, Z., Nodeh, H.R.Y., and Raeisi, S. (2023). The effects of ketogenic diet on beta-hydroxybutyrate, arachidonic acid, and oxidative stress in pediatric epilepsy. Epilepsy Behav. 140: 109106, https://doi.org/10.1016/j.yebeh.2023.109106.Suche in Google Scholar PubMed
Puchalska, P. and Crawford, P.A. (2021). Metabolic and signaling roles of ketone bodies in health and disease. Annu. Rev. Nutr. 41: 49–77, https://doi.org/10.1146/annurev-nutr-111120-111518.Suche in Google Scholar PubMed PubMed Central
Puttachary, S., Sharma, S., Stark, S., and Thippeswamy, T. (2015). Seizure-induced oxidative stress in temporal lobe epilepsy. Biomed. Res. Int. 2015: 745613, https://doi.org/10.1155/2015/745613.Suche in Google Scholar PubMed PubMed Central
Rana, A. and Musto, A.E. (2018). The role of inflammation in the development of epilepsy. J. Neuroinflamm. 15: 1–12, https://doi.org/10.1186/s12974-018-1192-7.Suche in Google Scholar PubMed PubMed Central
Ravizza, T., Gagliardi, B., Noé, F., Boer, K., Aronica, E., and Vezzani, A. (2008). Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. Neurobiol. Dis. 29: 142–160, https://doi.org/10.1016/j.nbd.2007.08.012.Suche in Google Scholar PubMed
Ravizza, T. and Vezzani, A. (2006). Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system. Neuroscience 137: 301–308, https://doi.org/10.1016/j.neuroscience.2005.07.063.Suche in Google Scholar PubMed
Rhyu, H.S., Cho, S.Y., and Roh, H.T. (2014). The effects of ketogenic diet on oxidative stress and antioxidative capacity markers of Taekwondo athletes. J. Exerc. Rehabil. 10: 362–366, https://doi.org/10.12965/jer.140178.Suche in Google Scholar PubMed PubMed Central
Rondanelli, M., Gasparri, C., Peroni, G., Faliva, M.A., Naso, M., Perna, S., Bazire, P., Sajuox, I., Maugeri, R., and Rigon, C. (2021). The potential roles of very low calorie, very low calorie ketogenic diets and very low carbohydrate diets on the gut microbiota composition. Front. Endocrinol. 12: 662591, https://doi.org/10.3389/fendo.2021.662591.Suche in Google Scholar PubMed PubMed Central
Ruskin, D.N., Kawamura, M., and Masino, S.A. (2020). Adenosine and ketogenic treatments. J. Caffeine Adenosine Res. 10: 104–109, https://doi.org/10.1089/caff.2020.0011.Suche in Google Scholar PubMed PubMed Central
Serrano, G., Lelutiu, N., Rojas, A., Cochi, S., Shaw, R., Makinson, C., Wang, D., FitzGerald, G., and Dingledine, R. (2011). Ablation of cyclooxygenase-2 in forebrain neurons is neuroprotective and dampens brain inflammation after status epilepticus. J. Neurosci. 31: 14850–14860, https://doi.org/10.1523/jneurosci.3922-11.2011.Suche in Google Scholar
Shimada, T., Takemiya, T., Sugiura, H., and Yamagata, K. (2014). Role of inflammatory mediators in the pathogenesis of epilepsy. Mediat. Inflamm. 2014: 901902, https://doi.org/10.1155/2014/901902.Suche in Google Scholar PubMed PubMed Central
Shin, E.-J., Jeong, J.H., Chung, Y.H., Kim, W.-K., Ko, K.-H., Bach, J.-H., Hong, J.-S., Yoneda, Y., and Kim, H.-C. (2011). Role of oxidative stress in epileptic seizures. Neurochem. Int. 59: 122–137, https://doi.org/10.1016/j.neuint.2011.03.025.Suche in Google Scholar PubMed PubMed Central
Shinoda, S., Skradski, S.L., Araki, T., Schindler, C.K., Meller, R., Lan, J.Q., Taki, W., Simon, R.P., and Henshall, D.C. (2003). Formation of a tumour necrosis factor receptor 1 molecular scaffolding complex and activation of apoptosis signal‐regulating kinase 1 during seizure‐induced neuronal death. Eur. J. Neurosci. 17: 2065–2076, https://doi.org/10.1046/j.1460-9568.2003.02655.x.Suche in Google Scholar PubMed
SM, T.P. and Rothwell, N. (2005). Interleukin-1 and neuronal injury. Nat. Rev. Immunol. 5: 629640.10.1038/nri1664Suche in Google Scholar PubMed
Stellwagen, D., Beattie, E.C., Seo, J.Y., and Malenka, R.C. (2005). Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-α. J. Neurosci. 25: 3219–3228, https://doi.org/10.1523/jneurosci.4486-04.2005.Suche in Google Scholar PubMed PubMed Central
Štros, M. (2010). HMGB proteins: interactions with DNA and chromatin. Biochim. Biophys. Acta Gene Regul. Mech. 1799: 101–113, https://doi.org/10.1016/j.bbagrm.2009.09.008.Suche in Google Scholar PubMed
Takemiya, T., Matsumura, K., Sugiura, H., Maehara, M., Yasuda, S., Uematsu, S., Akira, S., and Yamagata, K. (2010). Endothelial microsomal prostaglandin E synthase‐1 exacerbates neuronal loss induced by kainate. J. Neurosci. Res. 88: 381–390, https://doi.org/10.1002/jnr.22195.Suche in Google Scholar PubMed
Terrone, G., Frigerio, F., Balosso, S., Ravizza, T., and Vezzani, A. (2019). Inflammation and reactive oxygen species in status epilepticus: biomarkers and implications for therapy. Epilepsy Behav. 101: 106275, https://doi.org/10.1016/j.yebeh.2019.04.028.Suche in Google Scholar PubMed
Thambi, M., Nathan, J., Bailur, S., Unnikrishnan, M.K., Ballal, M., and Radhakrishnan, K. (2021). Is the antiseizure effect of ketogenic diet in children with drug-resistant epilepsy mediated through proinflammatory cytokines? Epilepsy Res 176: 106724, https://doi.org/10.1016/j.eplepsyres.2021.106724.Suche in Google Scholar PubMed
Tian, G.-F., Azmi, H., Takano, T., Xu, Q., Peng, W., Lin, J., Oberheim, N., Lou, N., Wang, X., Zielke, H.R., et al.. (2005). An astrocytic basis of epilepsy. Nat. Med. 11: 973–981, https://doi.org/10.1038/nm1277.Suche in Google Scholar PubMed PubMed Central
Van de Veerdonk, F.L., Netea, M.G., Dinarello, C.A., and Joosten, L.A. (2011). Inflammasome activation and IL-1β and IL-18 processing during infection. Trends Immunol. 32: 110–116, https://doi.org/10.1016/j.it.2011.01.003.Suche in Google Scholar PubMed
Vezzani, A. (2005). Inflammation and epilepsy. Epilepsy Curr. 5: 1–6, https://doi.org/10.1111/j.1535-7597.2005.05101.x.Suche in Google Scholar PubMed PubMed Central
Vezzani, A. (2010) Preventing epileptogenesis: antiinflammatory strategy. In: Paper presented at the epilepsia.Suche in Google Scholar
Vezzani, A., Auvin, S., Ravizza, T., and Aronica, E. (2012). Glia-neuronal interactions in ictogenesis and epileptogenesis: role of inflammatory mediators. In: Jasper’s basic mechanisms of the epilepsies [Internet], 4th ed.10.1093/med/9780199746545.003.0048Suche in Google Scholar
Vezzani, A., Moneta, D., Richichi, C., Aliprandi, M., Burrows, S.J., Ravizza, T., Perego, C., and De Simoni, M.G. (2002). Functional role of inflammatory cytokines and antiinflammatory molecules in seizures and epileptogenesis. Epilepsia 43: 30–35, https://doi.org/10.1046/j.1528-1157.43.s.5.14.x.Suche in Google Scholar PubMed
Viviani, B., Bartesaghi, S., Gardoni, F., Vezzani, A., Behrens, M., Bartfai, T., Binaglia, M., Corsini, E., Di Luca, M., Galli, C., et al.. (2003). Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J. Neurosci. 23: 8692–8700, https://doi.org/10.1523/jneurosci.23-25-08692.2003.Suche in Google Scholar PubMed PubMed Central
Walters, J.N., Bickford, J.S., Newsom, K.J., Beachy, D.E., Barilovits, S.J., Herlihy, J.-D., and Nick, H.S. (2012). Regulation of human microsomal prostaglandin E synthase-1 by IL-1β requires a distal enhancer element with a unique role for C/EBPβ. Biochem. J. 443: 561–571, https://doi.org/10.1042/bj20111801.Suche in Google Scholar PubMed
Wang, M., Zhang, X., Jia, W., Zhang, C., Boczek, T., Harding, M., Liu, Y., Li, M., Zhang, S., Lei, S., et al.. (2021). Circulating glutathione peroxidase and superoxide dismutase levels in patients with epilepsy: a meta-analysis. Seizure 91: 278–286, https://doi.org/10.1016/j.seizure.2021.07.001.Suche in Google Scholar PubMed
Wang, S., Cheng, Q., Malik, S., and Yang, J. (2000). Interleukin-1β inhibits γ-aminobutyric acid type A (GABAA) receptor current in cultured hippocampal neurons. J. Pharmacol. Exp. Ther. 292: 497–504.Suche in Google Scholar
Warren, E.C., Dooves, S., Lugarà, E., Damstra-Oddy, J., Schaf, J., Heine, V.M., Walker, M.C., and Williams, R.S.B. (2020). Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling. Proc. Natl. Acad. Sci. U. S. A. 117: 23617–23625, https://doi.org/10.1073/pnas.2008980117.Suche in Google Scholar PubMed PubMed Central
Weichhart, T., Costantino, G., Poglitsch, M., Rosner, M., Zeyda, M., Stuhlmeier, K.M., Kolbe, T., Stulnig, T.M., Hörl, W.H., Hengstschläger, M., et al.. (2008). The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29: 565–577, https://doi.org/10.1016/j.immuni.2008.08.012.Suche in Google Scholar PubMed
Weissberg, I., Wood, L., Kamintsky, L., Vazquez, O., Milikovsky, D.Z., Alexander, A., Oppenheim, H., Ardizzone, C., Becker, A., Frigerio, F., et al.. (2015). Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood–brain barrier dysfunction. Neurobiol. Dis. 78: 115–125, https://doi.org/10.1016/j.nbd.2015.02.029.Suche in Google Scholar PubMed PubMed Central
Wickström, R., Ygberg, S., Lindefeldt, M., and Dahlin, M. (2021). Altered cytokine levels in cerebrospinal fluid following ketogenic diet of children with refractory epilepsy. Epilepsy Res 177: 106775, https://doi.org/10.1016/j.eplepsyres.2021.106775.Suche in Google Scholar PubMed
Wisse, B.E., Ogimoto, K., and Schwartz, M.W. (2006). Role of hypothalamic interleukin-1β (IL-1β) in regulation of energy homeostasis by melanocortins. Peptides 27: 265–273, https://doi.org/10.1016/j.peptides.2005.08.020.Suche in Google Scholar PubMed
Xu, S., Tao, H., Cao, W., Cao, L., Lin, Y., Zhao, S.M., Xu, W., Cao, J., and Zhao, J.Y. (2021). Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis. Signal Transduct. Knowl. Environ. 6: 54, https://doi.org/10.1038/s41392-020-00411-4.Suche in Google Scholar PubMed PubMed Central
Yamagata, K., Andreasson, K.I., Kaufmann, W.E., Barnes, C.A., and Worley, P.F. (1993). Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron 11: 371–386, https://doi.org/10.1016/0896-6273(93)90192-t.Suche in Google Scholar PubMed
Yamanashi, T., Iwata, M., Kamiya, N., Tsunetomi, K., Kajitani, N., Wada, N., Iitsuka, T., Yamauchi, T., Miura, A., Pu, S., et al.. (2017). Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses. Sci. Rep. 7: 7677, https://doi.org/10.1038/s41598-017-08055-1.Suche in Google Scholar PubMed PubMed Central
Yang, R., Wen, J., Wei, W., Chen, H., Cao, D., Chen, L., Lu, X., Hu, Y., Huang, T., Li, B., et al.. (2022). Improving the effects of ketogenic diet therapy in children with drug-resistant epilepsy. Seizure 94: 183–188, https://doi.org/10.1016/j.seizure.2021.10.021.Suche in Google Scholar PubMed
Ye, Z.-C. and Sontheimer, H. (1996). Cytokine modulation of glial glutamate uptake: a possible involvement of nitric oxide. Neuroreport 7: 2181–2185, https://doi.org/10.1097/00001756-199609020-00025.Suche in Google Scholar PubMed
Zarnowska, I.M. (2020). Therapeutic use of the ketogenic diet in refractory epilepsy: what we know and what still needs to be learned. Nutrients 12: 2616, https://doi.org/10.3390/nu12092616.Suche in Google Scholar PubMed PubMed Central
Zeise, M., Espinoza, J., Morales, P., and Nalli, A. (1997). Interleukin-1β does not increase synaptic inhibition in hippocampal CA3 pyramidal and dentate gyrus granule cells of the rat in vitro. Brain Res. 768: 341–344, https://doi.org/10.1016/s0006-8993(97)00787-7.Suche in Google Scholar PubMed
Zhang, W., Guo, X., Chen, L., Chen, T., Yu, J., Wu, C., and Zheng, J. (2021). Ketogenic diets and cardio-metabolic diseases. Front. Endocrinol. 12: 753039, https://doi.org/10.3389/fendo.2021.753039.Suche in Google Scholar PubMed PubMed Central
Zhu, G., Okada, M., Yoshida, S., Mori, F., Ueno, S., Wakabayashi, K., and Kaneko, S. (2006). Effects of interleukin-1β on hippocampal glutamate and GABA releases associated with Ca2+-induced Ca2+ releasing systems. Epilepsy Res 71: 107–116, https://doi.org/10.1016/j.eplepsyres.2006.05.017.Suche in Google Scholar PubMed
Zhu, H., Bi, D., Zhang, Y., Kong, C., Du, J., Wu, X., Wei, Q., and Qin, H. (2022). Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations. Signal Transduct. Knowl. Environ. 7: 11, https://doi.org/10.1038/s41392-021-00831-w.Suche in Google Scholar PubMed PubMed Central
© 2024 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Studying the Alzheimer’s disease continuum using EEG and fMRI in single-modality and multi-modality settings
- Diversity of amyloid beta peptide actions
- Empowering brain cancer diagnosis: harnessing artificial intelligence for advanced imaging insights
- Diagnostic machine learning applications on clinical populations using functional near infrared spectroscopy: a review
- Exploring the latest findings on endovascular treatments for giant aneurysms: a review
- Evolving frontiers: endovascular strategies for the treatment of delayed cerebral ischemia
- Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet
Artikel in diesem Heft
- Frontmatter
- Studying the Alzheimer’s disease continuum using EEG and fMRI in single-modality and multi-modality settings
- Diversity of amyloid beta peptide actions
- Empowering brain cancer diagnosis: harnessing artificial intelligence for advanced imaging insights
- Diagnostic machine learning applications on clinical populations using functional near infrared spectroscopy: a review
- Exploring the latest findings on endovascular treatments for giant aneurysms: a review
- Evolving frontiers: endovascular strategies for the treatment of delayed cerebral ischemia
- Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet