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Ketogenic diets and the nervous system: a scoping review of neurological outcomes from nutritional ketosis in animal studies

Published online by Cambridge University Press:  28 June 2021

Rowena Field Open the ORCID record for Rowena Field [Opens in a new window] ,
Tara Field ,
Fereshteh Pourkazemi  and
Kieron Rooney
Rowena Field*
Affiliation:
The University of Sydney, Faculty of Medicine and Health, Sydney, Australia
Tara Field
Affiliation:
The New South Wales Ministry of Health (NSW Health), Sydney, Australia
Fereshteh Pourkazemi
Affiliation:
The University of Sydney, Faculty of Medicine and Health, Sydney, Australia
Kieron Rooney
Affiliation:
The University of Sydney, Faculty of Medicine and Health, Sydney, Australia
*
*Corresponding author: Rowena Field, email: [email protected]
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Abstract

Objectives:

Ketogenic diets have reported efficacy for neurological dysfunctions; however, there are limited published human clinical trials elucidating the mechanisms by which nutritional ketosis produces therapeutic effects. The purpose of this present study was to investigate animal models that report variations in nervous system function by changing from a standard animal diet to a ketogenic diet, synthesise these into broad themes, and compare these with mechanisms reported as targets in pain neuroscience to inform human chronic pain trials.

Methods:

An electronic search of seven databases was conducted in July 2020. Two independent reviewers screened studies for eligibility, and descriptive outcomes relating to nervous system function were extracted for a thematic analysis, then synthesised into broad themes.

Results:

In total, 170 studies from eighteen different disease models were identified and grouped into fourteen broad themes: alterations in cellular energetics and metabolism, biochemical, cortical excitability, epigenetic regulation, mitochondrial function, neuroinflammation, neuroplasticity, neuroprotection, neurotransmitter function, nociception, redox balance, signalling pathways, synaptic transmission and vascular supply.

Discussion:

The mechanisms presented centred around the reduction of inflammation and oxidative stress as well as a reduction in nervous system excitability. Given the multiple potential mechanisms presented, it is likely that many of these are involved synergistically and undergo adaptive processes within the human body, and controlled animal models that limit the investigation to a particular pathway in isolation may reach differing conclusions. Attention is required when translating this information to human chronic pain populations owing to the limitations outlined from the animal research.

Keywords

Ketogenic dietAnimalNeurologicalBeta-hydroxybutyrateInflammation
Type
Review Article
Information
Nutrition Research Reviews , Volume 35 , Issue 2 , December 2022 , pp. 268 - 281
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Nutrition Society

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References

Bosma-den Boer, M, van Wetten, M & Pruimboom, L (20) Chronic inflammatory diseases are stimulated by current lifestyle: how diet, stress levels and medication prevent our body from recovering. Nutr Metab 2012, 9, 1–14.Google Scholar
Shen, Y, Kapfhamer, D, Minnella, A, et al. (2017) Bioenergetic state regulates innate inflammatory responses through the transcriptional co-repressor CtBP. Nat Commun 8, 624.CrossRefGoogle ScholarPubMed
Kopp, W (2019) How Western diet and lifestyle drive the pandemic of obesity and civilization diseases. Diabetes Metab Syndr Obes 12, 2221–2236.Google ScholarPubMed
Ruskin, D (2016) Metabolic therapy and pain. In: Masino, S, ed. Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease. New York: Oxford University Press, 196–208.Google Scholar
Davis, J, Fournakis, N & Ellison, J (2021) Ketogenic diet for the treatment and prevention of dementia: a review. J Geriatr Psychiatry Neurol 34, 3–10.CrossRefGoogle ScholarPubMed
Camberos-Luna, L & Massieu, L (2020) Therapeutic strategies for ketosis induction and their potential efficacy for the treatment of acute brain injury and neurodegenerative diseases. Neurochem Int 133, 104614.CrossRefGoogle ScholarPubMed
Phillips, MCL, Murtagh, DKJ, Gilbertson, LJ, Asztely, FJS & Lynch, CDP (2018) Low-fat versus ketogenic diet in Parkinson’s disease: a pilot randomized controlled trial. Mov Disord 33, 1306–1314.CrossRefGoogle ScholarPubMed
Norwitz, N, Hu, M & Clarke, K (2019) The mechanisms by which the ketone body D-beta-hydroxybutyrate may improve the multiple cellular pathologies of Parkinson’s disease. Front Nutr 6, 63.CrossRefGoogle ScholarPubMed
Taylor, M, Sullivan, D, Mahnken, J, Burns, J & Swerdlow, R (2018) Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement 4, 28–36.Google ScholarPubMed
Morris, G, Puri, B, Carvalho, A, et al. (2020) Induced ketosis as a treatment for neuroprogressive disorders: food for thought? Int J Neuropsychopharmacol 23, 366–384.CrossRefGoogle ScholarPubMed
McDougall, A, Bayley, M & Munce, S (2018) The ketogenic diet as a treatment for traumatic brain injury: a scoping review. Brain Inj 32, 416–422.CrossRefGoogle ScholarPubMed
Li, R, Liu, Y, Liu, H & Li, J (2020) Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration. J Food Biochem 44, e13140.Google ScholarPubMed
Sadeghifar, F & Penry, V (2019) Mechanisms and uses of dietary therapy as a treatment for epilepsy: a review. Glob Adv Health Med 8, 2164956119874784.CrossRefGoogle ScholarPubMed
Masino, S & Rho, J (2019) Metabolism and epilepsy: ketogenic diets as a homeostatic link. Brain Res 1703, 26–30.Google ScholarPubMed
Mahmoud, S, Ho-Huang, E & Buhler, J (2020) Systematic review of ketogenic diet use in adult patients with status epilepticus. Epilepsia Open 5, 10–21.CrossRefGoogle ScholarPubMed
Ruskin, DN, Kawamura, M & Masino, SA (2009) Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet. PLoS One 4, e8349.CrossRefGoogle ScholarPubMed
Rho, J & Stafstrom, C (2012) The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol 3, 59.Google Scholar
Masino, S & Ruskin, D (2013) Ketogenic diets and pain. J Child Neurol 28, 993–1001.CrossRefGoogle ScholarPubMed
Schabrun, S, Elgueta-Cancino, E & Hodges, P (2017) Smudging of the motor cortex is related to the severity of low back pain. Spine 42, 1172–1178.Google Scholar
Schabrun, S, Christensen, S, Mrachacz-Kersting, N & Graven-Nielsen, T (2016) Motor cortex reorganization and impaired function in the transition to sustained muscle pain. Cereb Cortex 26, 1878–1890.CrossRefGoogle ScholarPubMed
Kuner, R & Flor, H (2017) Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci 18, 20–30.CrossRefGoogle ScholarPubMed
Elma, Ö, Yilmaz, S, Deliens, T, et al. (2020) Do nutritional factors interact with chronic musculoskeletal pain? A systematic review. J Clin Med 9, 702.CrossRefGoogle ScholarPubMed
Brain, K, Burrows, T, Rollo, M, et al. (2018) A systematic review and meta-analysis of nutrition interventions for chronic noncancer pain. J Hum Nutr Diet 32, 198–225.CrossRefGoogle ScholarPubMed
Field, R, Pourkazemi, F, Turton, J & Rooney, K (2020) Dietary interventions are beneficial for patients with chronic pain: a systematic review with meta-analysis. Pain Med doi: 10.1093/pm/pnaa1378 Google Scholar
Nijs, J, Elma, Ö, Yilmaz, S, et al. (2019) Nutritional neurobiology and central nervous system sensitisation: missing link in a comprehensive treatment for chronic pain? Br J Anaesth 123, 539–543.CrossRefGoogle Scholar
Kaushik, AS, Strath, LJ & Sorge, RE (2020) Dietary interventions for treatment of chronic pain: oxidative stress and inflammation. Pain Ther 9, 487–498.CrossRefGoogle ScholarPubMed
Hite, A, Cavan, D, Cywes, R, et al. Clinical guidelines for the prescription of carbohydrate restriction as a therapeutic intervention V1.1. Low Carb USA. https://www.lowcarbusa.org/clinical-guidelines/ Google Scholar
Newman, JC & Verdin, E (2014) Ketone bodies as signaling metabolites. Trends Endocrinol Metab 25, 42–52.CrossRefGoogle ScholarPubMed
Shimazu, T, Hirschey, MD, Newman, J, et al. (2013) Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211–214.CrossRefGoogle ScholarPubMed
Eendfeldt, A & Scher, B The science of low carb and keto. DietDoctor.com. https://www.dietdoctor.com/low-carb/science Accessed 29/10/2020.Google Scholar
Paoli, A, Rubini, A, Volek, J & Grimaldi, K (2013) Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr 67, 789–796.CrossRefGoogle ScholarPubMed
Youm, Y, Nguyen, K, Grant, R, et al. (2015) The ketone metabolite [beta]-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med 21, 263–269.CrossRefGoogle ScholarPubMed
Rho, J (2017) How does the ketogenic diet induce anti-seizure effects? Neurosci Lett 637(Suppl. C), 4–10.CrossRefGoogle ScholarPubMed
Miller, V, Villamena, F & Volek, J (2018) Nutritional ketosis and mitohormesis: potential implications for mitochondrial function and human health. J Nutr Metab 2018, 1–27.CrossRefGoogle ScholarPubMed
Ruskin, D & Masino, S (2012) The nervous system and metabolic dysregulation: emerging evidence converges on ketogenic diet therapy. Front Neurosci 6, 33.CrossRefGoogle ScholarPubMed
Peters, M, Godfrey, C, McInerney, P, et al. (2020) Chapter 11: scoping reviews. In: Aromataris, E & Munn, Z, eds. JBI Reviewers Manual 2020. The Joanna Briggs Institute. https://reviewersmanual.joannabriggs.org/ Google Scholar
Tricco, A, Lillie, E, Zarin, W, et al. (2018) PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 169, 467–473.CrossRefGoogle ScholarPubMed
Campbell, G, Senior, A & Bell-Anderson, K (2017) Metabolic effects of high glycaemic index diets: a systematic review and meta-analysis of feeding studies in mice and rats. Nutrients 9, 646.CrossRefGoogle ScholarPubMed
Auvinen, H, Romijn, J, Biermasz, N, et al. (2011) Effects of high fat diet on the basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review. Horm Metab Res 43, 899–906.Google ScholarPubMed
Hooijmans, CR & Ritskes-Hoitinga, M (2013) Progress in using systematic reviews of animal studies to improve translational research. PLoS Med 10, e1001482.CrossRefGoogle ScholarPubMed
Pound, P & Ritskes-Hoitinga, M (2020) Can prospective systematic reviews of animal studies improve clinical translation? J Transl Med 18, 15.CrossRefGoogle ScholarPubMed
Hernandez, AR, Hernandez, CM, Campos, KT, et al. (2017) The antiepileptic ketogenic diet alters hippocampal transporter levels and reduces adiposity in aged rats. J Gerontol A Biol Sci Med Sci 73, 450–458.CrossRefGoogle Scholar
Hernandez, A, Hernandez, C, Campos, K, et al. (2018) A ketogenic diet improves cognition and has biochemical effects in prefrontal cortex that are dissociable from hippocampus. Front Aging Neurosci 10, 391.Google ScholarPubMed
Hernandez, A, Hernandez, C, Truckenbrod, L, et al. (2019) Age and ketogenic diet have dissociable effects on synapse-related gene expression between hippocampal subregions. Front Aging Neurosci 11, 239.CrossRefGoogle ScholarPubMed
Lauritzen, KH, Hasan-Olive, MM, Regnell, CE, et al. (2016) A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. Neurobiol Aging 48, 34–47.CrossRefGoogle ScholarPubMed
Zhang, Y, Xu, K, Kerwin, T, LaManna, J & Puchowicz, M (2018) Impact of aging on metabolic changes in the ketotic rat brain: glucose, oxidative and 4-HNE metabolism. Vol 1072. TypeOxygen Transport to Tissue XL. Advances in Experimental Medicine and Biology. Thews O, LaManna J, Harrison D: Springer International Publishing.CrossRefGoogle Scholar
Beckett, T, Studzinski, C, Keller, J, Paul Murphy, M & Niedowicz, D (2013) A ketogenic diet improves motor performance but does not affect beta-amyloid levels in a mouse model of Alzheimer’s disease. Brain Res 1505, 61–67.CrossRefGoogle ScholarPubMed
Ma, D, Wang, AC, Parikh, I, et al. (2018) Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Sci Rep 8, 6670.Google ScholarPubMed
Roy, M, Nugent, S, Tremblay-Mercier, J, et al. (2012) The ketogenic diet increases brain glucose and ketone uptake in aged rats: a dual tracer PET and volumetric MRI study. Brain Res 1488, 14–23.CrossRefGoogle ScholarPubMed
Van der Auwera, I, Wera, S, Van Leuven, F & Henderson, ST (2005) A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab (Lond) 2, 28.CrossRefGoogle Scholar
Ahn, Y, Narous, M, Tobias, R, Rho, J & Mychasiuk, R (2014) The ketogenic diet modifies social and metabolic alterations identified in the prenatal valproic acid model of autism spectrum disorder. Dev Neurosci 36, 371–380.CrossRefGoogle ScholarPubMed
Ahn, Y, Sabouny, R, Villa, B, et al. (2020) Aberrant mitochondrial morphology and function in the BTBR mouse model of autism is improved by two weeks of ketogenic diet. Int J Mol Cell Med 21, 3266.Google ScholarPubMed
Dai, Y, Zhao, Y, Tomi, M, et al. (2017) Sex-specific life course changes in the neuro-metabolic phenotype of Glut3 null heterozygous mice: ketogenic diet ameliorates electroencephalographic seizures and improves sociability. Endocrinology 158, 936–949.CrossRefGoogle ScholarPubMed
Mychasiuk, R & Rho, J (2017) Genetic modifications associated with ketogenic diet treatment in the BTBR T+Tf/j mouse model of autism spectrum disorder. Autism Res 10, 456–471.CrossRefGoogle Scholar
Newell, C, Shutt, T, Ahn, Y, et al. (2016) Tissue specific impacts of a ketogenic diet on mitochondrial dynamics in the BTBRT+tf/j mouse. Front Physiol 7, 654.CrossRefGoogle ScholarPubMed
Newell, C, Johnsen, V, Yee, N, et al. (2017) Ketogenic diet leads to O-G1cNAc modification in the BTBRT + tf/j mouse model of autism. Biochim Biophys Acta Mol Basis Dis 1863, 2274–2281.CrossRefGoogle Scholar
Smith, J, Rho, J & Teskey, G (2016) Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder. Behav Brain Res 304, 67–70.Google ScholarPubMed
Tai, KK & Truong, DD (2007) Ketogenic diet prevents seizure and reduces myoclonic jerks in rats with cardiac arrest-induced cerebral hypoxia. Neurosci Lett 425, 34–38.CrossRefGoogle ScholarPubMed
Tai, K, Nguyen, N, Pham, L & Truong, D (2008) Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration. J Neural Transm 115, 1011–1017.CrossRefGoogle ScholarPubMed
Tai, K, Pham, L & Truong, D (2009) Intracisternal administration of glibenclamide or 5-hydroxydecanoate does not reverse the neuroprotective effect of ketogenic diet against ischemic brain injury-induced neurodegeneration. Brain Inj 23, 1081–1088.CrossRefGoogle Scholar
Yang, Q, Guo, M, Wang, X, et al. (2017) Ischemic preconditioning with a ketogenic diet improves brain ischemic tolerance through increased extracellular adenosine levels and hypoxia-inducible factors. Brain Res 1667, 11–18.CrossRefGoogle ScholarPubMed
Ruskin, DN, Suter, TACS, Ross, JL & Masino, SA (2013) Ketogenic diets and thermal pain: dissociation of hypoalgesia, elevated ketones, and lowered glucose in rats. J Pain 14, 467–474.CrossRefGoogle ScholarPubMed
Elamin, M, Ruskin, D, Masino, S & Sacchetti, P (2018) Ketogenic diet modulates NAD+- dependent enzymes and reduces DNA damage in hippocampus. Front Cell Neurosci 12, 263.CrossRefGoogle ScholarPubMed
Fukushima, A, Ogura, Y, Furuta, M, et al. (2015) Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats. Brain Res 1622, 36–42.CrossRefGoogle Scholar
Genzer, Y, Dadon, M, Burg, C, Chapnik, N & Froy, O (2016) Effect of dietary fat and the circadian clock on the expression of brain-derived neurotrophic factor (BDNF). Mol Cell Endocrinol 430, 49–55.CrossRefGoogle Scholar
Heischmann, S, Gano, L, Quinn, K, et al. (2018) Regulation of kynurenine metabolism by a ketogenic diet. J Lipid Res 59, 958–966.CrossRefGoogle ScholarPubMed
Huang, J, Li, Y, Wu, C, et al. (2019) The effect of ketogenic diet on behaviors and synaptic functions of naive mice. Brain Behav 9, e01246.CrossRefGoogle ScholarPubMed
Leino, RL, Gerhart, DZ, Duelli, R, Enerson, BE & Drewes, LR (2001) Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem Int 38, 519–527.CrossRefGoogle ScholarPubMed
Ling, Y, Wang, D, Sun, Y, Zhao, D & Ni, H (20) Neuro-behavioral status and the hippocampal expression of metabolic associated genes in wild-type rat following a ketogenic diet. Front Neurol 10, 65.CrossRefGoogle Scholar
Melo, TM, Nehlig, A & Sonnewald, U (2006) Neuronal-glial interactions in rats fed a ketogenic diet. Neurochem Int 48, 498–507.CrossRefGoogle ScholarPubMed
Milder, JB, Liang, L-P & Patel, M (2010) Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet. Neurobiol Dis 40, 238–244.CrossRefGoogle ScholarPubMed
Pifferi, F, Tremblay, S, Croteau, E, et al. (2011) Mild experimental ketosis increases brain uptake of 11C-acetoacetate and 18F-fluorodeoxyglucose: a dual-tracer PET imaging study in rats. Nutr Neurosci 142, 51–58.CrossRefGoogle Scholar
Rho, J, Sarnat, H, Sullivan, P, Robbins, C & Kim, D (2004) Lack of long-term histopathologic changes in brain and skeletal muscle of mice treated with a ketogenic diet. J Child Neurol 19, 555–557.Google ScholarPubMed
Roy, M, Beauvieux, M, Naulin, J, et al. (2015) Rapid adaptation of rat brain and liver metabolism to a ketogenic diet: an integrated study using H-1- and C-13-NMR spectroscopy. J Cereb Blood Flow Metab 35, 1154–1162.CrossRefGoogle Scholar
Samala, R, Klein, J & Borges, K (2011) The ketogenic diet changes metabolite levels in hippocampal extracellular fluid. Neurochem Int 58, 5–8.CrossRefGoogle ScholarPubMed
Selfridge, J, Wilkins, H, Lezi, E, et al. (2015) Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure. J Bioenerg Biomembr 47, 1–11.Google ScholarPubMed
Strandberg, J, Kondziella, D, Thorlin, T & Asztely, F (2008) Ketogenic diet does not disturb neurogenesis in the dentate gyrus in rats. Neuroreport 19, 1235–1237.CrossRefGoogle Scholar
Sullivan, PG, Rippy, NA, Dorenbos, K, et al. (2004) The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 55, 576–580.CrossRefGoogle ScholarPubMed
Sussman, D, Germann, J & Henkelman, M (2015) Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring. Brain Behav 5, e00300.CrossRefGoogle ScholarPubMed
Thio, L, Rensing, N, Maloney, S, et al. (2010) A ketogenic diet does not impair rat behavior or long-term potentiation. Epilepsia 51, 1619–1623.Google ScholarPubMed
Viggiano, A, Meccariello, R, Santoro, A, et al. (2019) A calorie-restricted ketogenic diet reduces cerebral cortex vascularization in prepubertal rats. Nutrients 11, 2681.CrossRefGoogle ScholarPubMed
Vizuete, AF, de Souza, DF, Guerra, MC, et al. (2013) Brain changes in BDNF and S100B induced by ketogenic diets in Wistar rats. Life Sci 92, 923–928.CrossRefGoogle ScholarPubMed
Wang, X, Liu, Q, Zhou, J, Wu, X & Zhu, Q (2017) Beta hydroxybutyrate levels in serum and cerebrospinal fluid under ketone body metabolism in rats. Exp Anim 66, 177–182.CrossRefGoogle ScholarPubMed
Zarnowski, T, Choragiewicz, T, Tulidowicz-Bielak, M, et al. (2012) Ketogenic diet increases concentrations of kynurenic acid in discrete brain structures of young and adult rats. J Neural Transm 119, 679–684.CrossRefGoogle ScholarPubMed
Zhang, Y, Zhang, S, Marin-Valencia, I & Puchowicz, M (2015) Decreased carbon shunting from glucose toward oxidative metabolism in diet-induced ketotic rat brain. J Neurochem 132, 301–312.CrossRefGoogle ScholarPubMed
Ziegler, DR, Ribeiro, LC, Hagenn, M, et al. (2003) Ketogenic diet increases glutathione peroxidase activity in rat hippocampus. Neurochem Res 28, 1793–1797.CrossRefGoogle ScholarPubMed
Morrison, C, Hill, C, DuVall, M, et al. (2020) Consuming a ketogenic diet leads to altered hypoglycemic counter-regulation in mice. J Diabetes Complications 34, 107557.CrossRefGoogle ScholarPubMed
Yamada, KA, Rensing, N & Thio, LL (2005) Ketogenic diet reduces hypoglycemia-induced neuronal death in young rats. Neurosci Lett 385, 210–214.CrossRefGoogle ScholarPubMed
Bough, K & Eagles, D (1999) A ketogenic diet increases the resistance to pentylenetetrazole-induced seizures in the rat. Epilepsia 40, 138–143.CrossRefGoogle ScholarPubMed
Bough, K, Valiyil, R, Han, FT & Eagles, D (1999) Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet. Epilepsy Res 35, 21–28.CrossRefGoogle ScholarPubMed
Bough, K, Matthews, P & Eagles, D (2000) A ketogenic diet has different effects upon seizures induced by maximal electroshock and by pentylenetetrazole infusion. Epilepsy Res 38, 105–114.CrossRefGoogle ScholarPubMed
Bough, K, Yao, S & Eagles, D (2000) Higher ketogenic diet ratios confer protection from seizures without neurotoxicity. Epilepsy Res 38, 15–25.Google ScholarPubMed
Bough, K, Gudi, K, Han, F, Rathod, A & Eagles, D (2002) An anticonvulsant profile of the ketogenic diet in the rat. Epilepsy Res 50, 313–325.CrossRefGoogle ScholarPubMed
Bough, K, Schwartzkroin, P & Rho, J (2003) Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo. Epilepsia 44, 752–760.CrossRefGoogle ScholarPubMed
Bough, K, Wetherington, J, Hassel, B, et al. (2006) Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 60, 223–235.CrossRefGoogle ScholarPubMed
Bough, K, Paquet, M, Pare, J, et al. (2007) Evidence against enhanced glutamate transport in the anticonvulsant mechanism of the ketogenic diet. Epilepsy Res 74, 232–236.CrossRefGoogle ScholarPubMed
Bough, K (2008) Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet. Epilepsia 49, 91–93.Google ScholarPubMed
Calderón, N, Betancourt, L, Hernández, L & Rada, P (2017) A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: a microdialysis study. Neurosci Lett 642, 158–162.CrossRefGoogle ScholarPubMed
Cheng, C, Kelley, B, Wang, J, et al. (2003) A ketogenic diet increases brain insulin-like growth factor receptor and glucose transporter gene expression. Endocrinology 144, 2676–2682.CrossRefGoogle ScholarPubMed
Cheng, C, Hicks, K, Wang, J, Eagles, D & Bondy, C (2004) Caloric restriction augments brain glutamic acid decarboxylase-65 and -67 expression. J Neurosci Res 77, 270–276.CrossRefGoogle ScholarPubMed
Church, WH, Adams, RE & Wyss, LS (2014) Ketogenic diet alters dopaminergic activity in the mouse cortex. Neurosci Lett 571, 1–4.CrossRefGoogle ScholarPubMed
Chwiej, J, Patulska, A, Skoczen, A, et al. (2015) Elemental changes in the hippocampal formation following two different formulas of ketogenic diet: an X-ray fluorescence microscopy study. J Biol Inorg Chem 20, 1277–1286.CrossRefGoogle ScholarPubMed
Chwiej, J, Skoczen, A, Matusiak, K, et al. (2015) The influence of the ketogenic diet on the elemental and biochemical compositions of the hippocampal formation. Epilepsy Behav 49, 40–46.CrossRefGoogle ScholarPubMed
Chwiej, J, Patulska, A, Skoczen, A, et al. (2017) Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation. J Trace Elem Med Biol 42, 50–58.CrossRefGoogle ScholarPubMed
Cullingford, T, Eagles, D & Sato, H (2002) The ketogenic diet upregulates expression of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in rat brain. Epilepsy Res 49, 99–107.CrossRefGoogle ScholarPubMed
Dupuis, N, Curatolo, N, Benoist, J & Auvin, S (2015) Ketogenic diet exhibits anti-inflammatory properties. Epilepsia 56, e95–98.CrossRefGoogle ScholarPubMed
Dutton, S, Sawyer, N, Kalume, F, et al. (2011) Protective effect of the ketogenic diet in Scn1a mutant mice. Epilepsia 52, 2050–2056.CrossRefGoogle ScholarPubMed
Forero-Quintero, LS, Deitmer, JW & Becker, HM (2017) Reduction of epileptiform activity in ketogenic mice: the role of monocarboxylate transporters. Sci Rep 7, 4900.CrossRefGoogle ScholarPubMed
Gama, I, Trindade-Filho, E, Oliveira, S, et al. (2015) Effects of ketogenic diets on the occurrence of pilocarpine-induced status epilepticus of rats. Metab Brain Dis 30, 93–98.CrossRefGoogle ScholarPubMed
Gietzen, DW, Lindstrom, SH, Sharp, JW, Teh, PS & Donovan, MJ (2018) Indispensable amino acid-deficient diets induce seizures in ketogenic diet-fed rodents, demonstrating a role for amino acid balance in dietary treatments for epilepsy. J Nutr 148, 480–489.CrossRefGoogle ScholarPubMed
Godlevskii, LS, Polyasny, VO, Ovchinnikova, OG, et al. (2012) Modulation of the state of the antiepileptic cerebral system by the influence of a ketogenic diet under conditions of the resistant epileptic syndrome. Neurophysiology 43, 503–506.CrossRefGoogle Scholar
Gomez-Lira, G, Mendoza-Torreblanca, J & Granados-Rojas, L (2011) Ketogenic diet does not change NKCC1 and KCC2 expression in rat hippocampus. Epilepsy Res 96, 166–171.CrossRefGoogle Scholar
Hansen, SL, Nielsen, AH, Knudsen, KE, et al. (2009) Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus. Neurochem Int 54, 199–204.CrossRefGoogle ScholarPubMed
Harney, J, Madara, J, Madara, J & I’Anson, H (2002) Effects of acute inhibition of fatty acid oxidation on latency to seizure and concentrations of beta hydroxybutyrate in plasma of rats maintained on calorie restriction and/or the ketogenic diet. Epilepsy Res 49, 239–246.CrossRefGoogle ScholarPubMed
Hartman, A, Lyle, M, Rogawski, M & Gasior, M (2008) Efficacy of the ketogenic diet in the 6-Hz seizure test. Epilepsia 49, 334–339.CrossRefGoogle ScholarPubMed
Hartman, A, Zheng, X, Bergbower, E, Kennedy, M & Hardwick, J (2010) Seizure tests distinguish intermittent fasting from the ketogenic diet. Epilepsia 51, 1395–1402.CrossRefGoogle ScholarPubMed
Hasan-Olive, MM, Lauritzen, KH, Ali, M, et al. (2019) A ketogenic diet improves mitochondrial biogenesis and bioenergetics via the PGC1alpha-SIRT3-UCP2 axis. Neurochem Res 44, 22–37.CrossRefGoogle ScholarPubMed
Hori, A, Tandon, P, Holmes, G & Stafstrom, C (1997) Ketogenic diet: effects on expression of kindled seizures and behavior in adult rats. Epilepsia 38, 750–758.CrossRefGoogle ScholarPubMed
Hu, X, Cheng, X, Fei, J & Xiong, Z (2011) Neuron-restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet. Epilepsia 52, 1609–1616.CrossRefGoogle Scholar
Jarrett, SG, Milder, JB, Liang, LP & Patel, M (2008) The ketogenic diet increases mitochondrial glutathione levels. J Neurochem 106, 1044–1051.CrossRefGoogle ScholarPubMed
Jeon, BT, Lee, DH, Kim, KH, et al. (2009) Ketogenic diet attenuates kainic acid-induced hippocampal cell death by decreasing AMPK/ACC pathway activity and HSP70. Neurosci Lett 453, 49–53.CrossRefGoogle ScholarPubMed
Jeong, H, Kim, H, Kim, Y, et al. (2010) The ketogenic diet suppresses the cathepsin E expression induced by kainic acid in the rat brain. Yonsei Med J 51, 653–660.CrossRefGoogle ScholarPubMed
Jeong, E, Jeon, B, Shin, H, et al. (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.CrossRefGoogle ScholarPubMed
Jiang, Y, Yang, Y, Wang, S, et al. (2012) Ketogenic diet protects against epileptogenesis as well as neuronal loss in amygdaloid-kindling seizures. Neurosci Lett 508, 22–26.CrossRefGoogle ScholarPubMed
Kawamura, M, Ruskin, D, Geiger, J, Boison, D & Masino, S (2014) Ketogenic diet sensitizes glucose control of hippocampal excitability. J Lipid Res 55, 2254–2260.CrossRefGoogle ScholarPubMed
Knowles, S, Budney, S, Deodhar, M, et al. (2018) Ketogenic diet regulates the antioxidant catalase via the transcription factor PPARgamma2. Epilepsy Res 147, 71–74.CrossRefGoogle ScholarPubMed
Kobow, K, Kaspi, A, Harikrishnan, K, et al. (2013) Deep sequencing reveals increased DNA methylation in chronic rat epilepsy. Acta Neuropathol 126, 741–756.CrossRefGoogle ScholarPubMed
Koranda, JL, Ruskin, DN, Masino, SA & Blaise, JH (2011) A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats. J Neurophysiol 106, 662–666.CrossRefGoogle ScholarPubMed
Kresyun, V, Polyasny, V, Godovan, V & Godlevsky, L (2013) Changes in brain cortex sensitivity to epileptogens under conditions of ketogenic diet. Bull Exp Biol Med 154, 457–459.CrossRefGoogle ScholarPubMed
Kwon, Y, Jeong, S, Kim, D, Choi, E & Son, B (2008) Effects of the ketogenic diet on neurogenesis after kainic acid-induced seizures in mice. Epilepsy Res 78, 186–194.Google ScholarPubMed
Likhodii, S, Musa, K, Mendonca, A, et al. (2000) Dietary fat, ketosis, and seizure resistance in rats on the ketogenic diet. Epilepsia 41, 1400–1410.CrossRefGoogle ScholarPubMed
Lin, GW, Lu, P, Zeng, T, et al. (2017) GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions. Neuropharmacology 113, 480–489.CrossRefGoogle ScholarPubMed
Linard, B, Ferrandon, A, Koning, E, Nehlig, A & Raffo, E (2010) Ketogenic diet exhibits neuroprotective effects in hippocampus but fails to prevent epileptogenesis in the lithium-pilocarpine model of mesial temporal lobe epilepsy in adult rats. Epilepsia 51, 1829–1836.CrossRefGoogle ScholarPubMed
Luan, G, Zhao, Y, Zhai, F, Chen, Y & Li, T (2012) Ketogenic diet reduces Smac/Diablo and cytochrome c release and attenuates neuronal death in a mouse model of limbic epilepsy. Brain Res Bull 89, 79–85.CrossRefGoogle Scholar
Lusardi, T, Akula, K, Coffman, S, et al. (2015) Ketogenic diet prevents epileptogenesis and disease progression in adult mice and rats. Neuropharmacology 99, 500–509.CrossRefGoogle ScholarPubMed
Mantis, J, Meidenbauer, J, Zimick, N, Centeno, N & Seyfried, T (2014) Glucose reduces the anticonvulsant effects of the ketogenic diet in EL mice. Epilepsy Res 108, 1137–1144.CrossRefGoogle ScholarPubMed
Martillotti, J, Weinshenker, D, Liles, L & Eagles, D (2006) A ketogenic diet and knockout of the norepinephrine transporter both reduce seizure severity in mice. Epilepsy Res 68, 207–211.CrossRefGoogle ScholarPubMed
Masino, S, Li, T, Theofilas, P, et al. (2011) A ketogenic diet suppresses seizures in mice through adenosine A 1 receptors. J Clin Invest 121, 2679–2683.CrossRefGoogle Scholar
McDaniel, S, Rensing, N, Thio, L, Yamada, K & Wong, M (2011) The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 52, e7–e11.CrossRefGoogle ScholarPubMed
Melo, IT, Rego, EM, Bueno, NB, et al. (2018) Ketogenic diet based on extra virgin coconut oil has no effects in young Wistar rats with pilocarpine-induced epilepsy. Lipids 53, 251–254.CrossRefGoogle ScholarPubMed
Muller-Schwarze, AB, Tandon, P, Liu, Z, et al. (1999) Ketogenic diet reduces spontaneous seizures and mossy fiber sprouting in the kainic acid model. Neuroreport 10, 1517–1522.CrossRefGoogle ScholarPubMed
Nakazawa, M, Kodama, S & Matsuo, T (1983) Effects of ketogenic diet on electroconvulsive threshold and brain contents of adenosine nucleotides. Brain Dev 5, 375–380.CrossRefGoogle ScholarPubMed
Ni, H, Zhao, D & Tian, T (2016) Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures. Epilepsy Res 120, 13–18.CrossRefGoogle ScholarPubMed
Noh, H, Kim, Y, Lee, H, et al. (2003) The protective effect of a ketogenic diet on kainic acid-induced hippocampal cell death in the male ICR mice. Epilepsy Res 53, 119–128.Google ScholarPubMed
Noh, HS, Lee, HP, Kim, DW, et al. (2004) A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet. Mol Brain Res 129, 80–87.Google ScholarPubMed
Noh, H, Kang, S, Kim, D, et al. (2005) Ketogenic diet increases calbindin-D28k in the hippocampi of male ICR mice with kainic acid seizures. Epilepsy Res 65, 153–159.CrossRefGoogle ScholarPubMed
Noh, H, Kim, D, Kang, S, Cho, G & Choi, W (2005) Ketogenic diet prevents clusterin accumulation induced by kainic acid in the hippocampus of male ICR mice. Brain Res 1042, 114–118.CrossRefGoogle ScholarPubMed
Noh, H, Kim, D, Cho, G, Choi, W & Kang, S (2006) Increased nitric oxide caused by the ketogenic diet reduces the onset time of kainic acid-induced seizures in ICR mice. Brain Res 1075, 193–200.CrossRefGoogle ScholarPubMed
Noh, HS, Kim, DW, Kang, SS, et al. (2006) Ketogenic diet decreases the level of proenkephalin mRNA induced by kainic acid in the mouse hippocampus. Neurosci Lett 395, 87–92.CrossRefGoogle ScholarPubMed
Nylen, K, Likhodii, S, Abdelmalik, P, Clarke, J & Burnham, W (2005) A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats. Epilepsia 46, 1198–1204.CrossRefGoogle Scholar
Nylen, K, Likhodii, S, Hum, K & Burnham, W (2006) A ketogenic diet and diallyl sulfide do not elevate afterdischarge thresholds in adult kindled rats. Epilepsy Res 71, 23–31.CrossRefGoogle Scholar
de Almeida Rabello Oliveira, M, da Rocha Ataíde, T, de Oliveira, SL, et al. (2008) Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats. Neurosci Lett 434, 66–70.CrossRefGoogle ScholarPubMed
Olson, C, Vuong, H, Yano, J, et al. (2018) The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell 173, 1728–1741.CrossRefGoogle ScholarPubMed
Raffo, E, Francois, J, Ferrandon, A, Koning, E & Nehlig, A (2008) Calorie-restricted ketogenic diet increases thresholds to all patterns of pentylenetetrazol-induced seizures: critical importance of electroclinical assessment. Epilepsia 49, 320–328.CrossRefGoogle ScholarPubMed
Rho, J, Kim, D, Robbins, C, Anderson, G & Schwartzkroin, P (1999) Age-dependent differences in flurothyl seizure sensitivity in mice treated with a ketogenic diet. Epilepsy Res 37, 233–240.CrossRefGoogle ScholarPubMed
Samala, R, Willis, S, Borges, K (2008) Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models. Epilepsy Res 81, 119–127.CrossRefGoogle ScholarPubMed
Silva, MC, Rocha, J, Pires, CS, et al. (2005) Transitory gliosis in the CA3 hippocampal region in rats fed on a ketogenic diet. Nutr Neurosci 8, 259–264.CrossRefGoogle ScholarPubMed
Simeone, K, Wilke, J, Milligan, H, et al. (2009) Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1-null mice. Epilepsia 50, 2027–2034.CrossRefGoogle Scholar
Simeone, K, Matthews, S, Rho, J & Simeone, T (2016) Ketogenic diet treatment increases longevity in Kcna1-null mice, a model of sudden unexpected death in epilepsy. Epilepsia 57, e178–e182.CrossRefGoogle Scholar
Simeone, T, Samson, K, Matthews, S & Simeone, K (2014) In vivo ketogenic diet treatment attenuates pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices from epileptic K(v)1.1 alpha knockout mice. Epilepsia 55, E44–E49.CrossRefGoogle Scholar
Simeone, T, Matthews, S, Samson, K & Simeone, K (2017) Regulation of brain PPARgamma2 contributes to ketogenic diet anti-seizure efficacy. Exp Neurol 287, 54–64.CrossRefGoogle ScholarPubMed
Stafstrom, C, Wang, C & Jensen, F (1999) Electrophysiological observations in hippocampal slices from rats treated with the ketogenic diet. Dev Neurosci 21, 393–399.CrossRefGoogle ScholarPubMed
Su, S, Cilio, M, Sogawa, Y, et al. (2000) Timing of ketogenic diet initiation in an experimental epilepsy model. Brain Res 125, 131–138.CrossRefGoogle Scholar
Szot, P, Weinshenker, D, Rho, J, Storey, T & Schwartzkroin, P (2001) Norepinephrine is required for the anticonvulsant effect of the ketogenic diet. Brain Res Dev Brain Res 129, 211–214.CrossRefGoogle ScholarPubMed
Tabb, K, Szot, P, White, S, Liles, L & Weinshenker, D (2004) The ketogenic diet does not alter brain expression of orexigenic neuropeptides. Epilepsy Res 62, 35–39.CrossRefGoogle Scholar
Thavendiranathan, P, Mendonca, A, Dell, C, et al. (2000) The MCT ketogenic diet: effects on animal seizure models. Exp Neurol 161, 696–703.CrossRefGoogle ScholarPubMed
Thavendiranathan, P, Chow, C, Cunnane, S & Burnham, W (2003) The effect of the ‘classic’ ketogenic diet on animal seizure models. Brain Res 959, 206–213.CrossRefGoogle ScholarPubMed
Tian, T, Ni, H & Sun, B (2015) Neurobehavioral deficits in a rat model of recurrent neonatal seizures are prevented by a ketogenic diet and correlate with hippocampal zinc/lipid transporter signals. Biol Trace Elem Res 167, 251–258.CrossRefGoogle Scholar
Tian, T, Li, LL, Zhang, S & Ni, H (2016) Long-term effects of ketogenic diet on subsequent seizure-induced brain injury during early adulthood: relationship of seizure thresholds to zinc transporter-related gene expressions. Biol Trace Elem Res 174, 369–376.CrossRefGoogle ScholarPubMed
Todorova, M, Tandon, P, Madore, R, Stafstrom, C & Seyfried, T (2000) The ketogenic diet inhibits epileptogenesis in EL mice: a genetic model for idiopathic epilepsy. Epilepsia 41, 933–940.CrossRefGoogle ScholarPubMed
Viggiano, A, Stoddard, M, Pisano, S, et al. (2016) Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats. Brain Res Bull 125, 168–172.Google ScholarPubMed
Wang, S, Ding, Y, Ding, X-Y, et al. (2016) Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms. Neurosci Lett 614, 1–6.CrossRefGoogle ScholarPubMed
Wang, B, Hou, Q, Lu, Y, et al. (2018) Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures. Brain Res 1678, 106–115.CrossRefGoogle ScholarPubMed
Xu, X, Sun, R & Jin, R (2008) The effect of the ketogenic diet on hippocampal GluR(5) and GluR(6) mRNA expression and Q/R site editing in the kainate-induced epilepsy model. Epilepsy Behav 13, 445–448.CrossRefGoogle ScholarPubMed
Zarnowska, I, Luszczki, JJ, Zarnowski, T, et al. (2017) Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice. Metab Brain Dis 32, 351–358.CrossRefGoogle ScholarPubMed
Ziegler, DR, Araujo, E, Rotta, LN, Perry, ML & Goncalves, CA (2002) A ketogenic diet increases protein phosphorylation in brain slices of rats. J Nutr 132, 483–487.CrossRefGoogle ScholarPubMed
Ziegler, DR, Oliveira, DL, Pires, C, et al. (2004) Ketogenic diet fed rats have low levels of S100B in cerebrospinal fluid. Neurosci Res 50, 375–379.CrossRefGoogle ScholarPubMed
Blaise, H, Ruskin, D, Koranda, J & Masino, S (2015) Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats. Physiol Rep 3, e12411.CrossRefGoogle ScholarPubMed
Masino, S, Freedgood, N, Reichert, H, et al. (2019) Dietary intervention for canine epilepsy: two case reports. Epilepsia Open 4, 193–199.CrossRefGoogle ScholarPubMed
Kephart, WC, Mumford, PW, Mao, XS, et al. (2017) The 1-week and 8-month effects of a ketogenic diet or ketone salt supplementation on multi-organ markers of oxidative stress and mitochondrial function in rats. Nutrients 9, 1019.CrossRefGoogle ScholarPubMed
Mohamed, H, El-Swefy, S, Rashed, L & Abd El-Latif, S (2010) Biochemical effect of a ketogenic diet on the brains of obese adult rats. J Clin Neurosci 17, 899–904.CrossRefGoogle ScholarPubMed
Hargrave, S, Davidson, T, Lee, T & Kinzig, K (2015) Brain and behavioral perturbations in rats following Western diet access. Appetite 93, 35–43.CrossRefGoogle ScholarPubMed
Kim, DY, Hao, J, Liu, R, et al. (2012) Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS One 7, e35476.CrossRefGoogle Scholar
Stumpf, S, Berghoff, S, Trevisiol, A, et al. (2019) Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease. Acta Neuropathol 138, 147–161.CrossRefGoogle ScholarPubMed
Myers, T, Langston, J (2011) Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity. Neurotoxicology 32, 342–349.CrossRefGoogle ScholarPubMed
Bernardo-Colon, A, Vest, V, Clark, A, et al. (2018) Antioxidants prevent inflammation and preserve the optic projection and visual function in experimental neurotrauma. Cell Death Dis 9, 1097.CrossRefGoogle ScholarPubMed
Harun-Or-Rashid, M, Pappenhagen, N, Palmer, PG, et al. (2018) Structural and functional rescue of chronic metabolically stressed optic nerves through respiration. J Neurosci 38, 5122–5139.CrossRefGoogle ScholarPubMed
Harun-Or-Rashid, M & Inman, DM (2018) Reduced AMPK activation and increased HCAR activation drive anti-inflammatory response and neuroprotection in glaucoma. J Neuroinflammation 15, 313.CrossRefGoogle ScholarPubMed
Zarnowski, T, Choragiewicz, T, Schuettauf, F, et al. (2015) Ketogenic diet attenuates NMDA-induced damage to rat’s retinal ganglion cells in an age-dependent manner. Ophthalmic Res 53, 162–167.CrossRefGoogle Scholar
Cheng, B, Yang, X, An, L, et al. (2009) Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson’s disease. Brain Res 1286, 25–31.CrossRefGoogle Scholar
Yang, X & Cheng, B (2010) Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity. J Mol Neurosci 42, 145–153.CrossRefGoogle ScholarPubMed
Cooper, M, McCoin, C, Pei, D, et al. (2018) Reduced mitochondrial reactive oxygen species production in peripheral nerves of mice fed a ketogenic diet. Exp Physiol 103, 1206–1212.CrossRefGoogle ScholarPubMed
Cooper, M, Menta, B, Perez-Sanchez, C, et al. (2018) A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice. Exp Neurol 306, 149–157.CrossRefGoogle ScholarPubMed
Liskiewicz, A, Wlaszczuk, A, Gendosz, D, et al. (2016) Sciatic nerve regeneration in rats subjected to ketogenic diet. Nutr Neurosci 1, 116–124.CrossRefGoogle Scholar
Kong, G, Huang, Z, Ji, W, et al. (2017) The ketone metabolite beta-hydroxybutyrate attenuates oxidative stress in spinal cord injury by suppression of Class I histone deacetylases. J Neurotrauma 34, 2645–2655.CrossRefGoogle ScholarPubMed
Lu, Y, Yang, Y-Y, Zhou, M-W, et al. (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.CrossRefGoogle ScholarPubMed
Streijger, F, Plunet, WT, Lee, JH, et al. (2013) Ketogenic diet improves forelimb motor function after spinal cord injury in rodents. PLoS One 8, e78765.CrossRefGoogle ScholarPubMed
Wang, X, Wu, X, Liu, Q, et al. (2017) Ketogenic metabolism inhibits histone deacetylase (HDAC) and reduces oxidative stress after spinal cord injury in rats. Neuroscience 366, 36–43.CrossRefGoogle ScholarPubMed
Guo, M, Wang, X, Zhao, Y, et al. (2018) Ketogenic diet improves brain ischemic tolerance and inhibits NLRP3 inflammasome activation by preventing Drp1-mediated mitochondrial fission and endoplasmic reticulum stress. Front Mol Neurosci 11, 86.CrossRefGoogle ScholarPubMed
Puchowicz, M, Zechel, J, Valerio, J, et al. (2008) Neuroprotection in diet-induced ketotic rat brain after focal ischemia. J Cereb Blood Flow Metab 28, 1907–1916.CrossRefGoogle ScholarPubMed
Rahman, M, Muhammad, S, Khan, MA, et al. (2014) The β-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages. Nat Commun 5, 1–11.CrossRefGoogle ScholarPubMed
Deng-Bryant, Y, Prins, M, Hovda, D & Harris, N (2011) Ketogenic diet prevents alterations in brain metabolism in young but not adult rats after traumatic brain injury. J Neurotrauma 28, 1813–1825.CrossRefGoogle Scholar
Greco, T, Glenn, T, Hovda, D & Prins, M (2016) Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity. J Cereb Blood Flow Metab 36, 1603–1613.CrossRefGoogle ScholarPubMed
Hu, Z, Wang, H, Jin, W & Yin, H (2009) Ketogenic diet reduces cytochrome c release and cellular apoptosis following traumatic brain injury in juvenile rats. Ann Clin Lab Sci 39, 76–83.Google ScholarPubMed
Hu, Z, Wang, H, Qiao, L, et al. (2009) The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. Brain Inj 23, 459–465.CrossRefGoogle ScholarPubMed
Prins, M, Fujima, L & Hovda, D (2005) Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury. J Neurosci Res 82, 413–420.CrossRefGoogle ScholarPubMed
Prins, ML & Hovda, DA (2009) The effects of age and ketogenic diet on local cerebral metabolic rates of glucose after controlled cortical impact injury in rats. J Neurotrauma 26, 1083–1093.CrossRefGoogle ScholarPubMed
Salberg, S, Weerwardhena, H, Collins, R, Reimer, R & Mychasiuk, R (2019) The behavioural and pathophysiological effects of the ketogenic diet on mild traumatic brain injury in adolescent rats. Behav Brain Res 376, 112225.CrossRefGoogle ScholarPubMed
Schwartzkroin, P, Wenzel, H, Lyeth, B, et al. (2010) Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury? Epilepsy Res 92, 74–84.CrossRefGoogle ScholarPubMed
Zhang, F, Wu, H, Jin, Y & Zhang, X (2018) Proton magnetic resonance spectroscopy (H1-MRS) study of the ketogenic diet on repetitive mild traumatic brain injury in adolescent rats and its effect on neurodegeneration. World Neurosurg 120, e1193–e1202.CrossRefGoogle ScholarPubMed
Yang, H, Shan, W, Zhu, F, Wu, J & Wang, Q (2019) Ketone bodies in neurological diseases: focus on neuroprotection and underlying mechanisms. Front Neurol 10, 585.Google ScholarPubMed
Morris, G, Puri, BK, Maes, M, et al. (2020) The role of microglia in neuroprogressive disorders: mechanisms and possible neurotherapeutic effects of induced ketosis. Prog Neuropsychopharmacol Biol Psychiatry 99, 109858.CrossRefGoogle ScholarPubMed
Spite, M, Clària, J & Serhan, C (2014) Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell Metab 19, 21–36.CrossRefGoogle ScholarPubMed
Totsch, S, Waite, M & Sorge, R (2015) Dietary influence on pain via the immune system. In: Theodore, JP & Gregory, D, eds. Progress in Molecular Biology and Translational Science. Vol 131. Cambridge: Academic Press, 435–469.Google Scholar
Farrell, S, de Zoete, R, Cabot, P & Sterling, M (2020) Systemic inflammatory markers in neck pain: a systematic review with meta-analysis. Eur J Pain 24, 1666–1696.CrossRefGoogle ScholarPubMed
Schistad, EI, Stubhaug, A, Furberg, A-S, Engdahl, BL & Nielsen, CS (2017) C-reactive protein and cold-pressor tolerance in the general population: the Tromsø Study. Pain 158, 1280–1288.CrossRefGoogle ScholarPubMed
Dupuis, N (2016) Anti- inflammatory effects of a ketogenic diet – implications for new indications. In: Masino, SA, ed. Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease. Oxford, USA: Oxford University Press, Incorporated, 147–155.Google Scholar
Meeus, M, Nijs, J, Hermans, L, Goubert, D & Calders, P (2013) The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets 17, 1081–1089.CrossRefGoogle ScholarPubMed
Löffler, M, Gamroth, C, Becker, S & Flor, H (2020) Chronic pain as a neglected core symptom in mitochondrial diseases. Neurology 94, 357–359.CrossRefGoogle ScholarPubMed
Van Den Ameele, J, Fuge, J, Pitceathly, RD, et al. (2020) Chronic pain is common in mitochondrial disease. Neuromuscul Disord 30, 413–419.CrossRefGoogle ScholarPubMed
Sui, B-d, Xu, T-q, Liu, J-w, et al. (2013) Understanding the role of mitochondria in the pathogenesis of chronic pain. Postgrad Med J 89, 709–714.CrossRefGoogle ScholarPubMed
Parker, R, Lewis, G, Rice, D & McNair, P (2016) Is motor cortical excitability altered in people with chronic pain? A systematic review and meta-analysis. Brain Stimul 9, 488–500.CrossRefGoogle ScholarPubMed
Neblett, R, Cohen, H, Choi, Y, et al. (2013) The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain 14, 438–445.CrossRefGoogle Scholar
Rezaei, S, Abdurahman, AA, Saghazadeh, A, Badv, RS & Mahmoudi, M (2019) Short-term and long-term efficacy of classical ketogenic diet and modified Atkins diet in children and adolescents with epilepsy: a systematic review and meta-analysis. Nutr Neurosci 22, 317–334.CrossRefGoogle ScholarPubMed
Peek, AL, Rebbeck, T, Puts, NAJ, et al. (2020) Brain GABA and glutamate levels across pain conditions: a systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool. Neuroimage 210, 116532.CrossRefGoogle ScholarPubMed
Schugar, RC, Huang, X, Moll, AR, Brunt, EM & Crawford, PA (2013) Role of choline deficiency in the fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet. PLoS One 8, e74806.CrossRefGoogle ScholarPubMed
Anez-Bustillos, L, Dao, D, Finkelstein, A, et al. (2019) Metabolic and inflammatory effects of an omega-3 fatty acid-based eucaloric ketogenic diet in mice with endotoxemia. J Parenter Enteral Nutr 43, 986–997.CrossRefGoogle ScholarPubMed
Burma, N, Leduc-Pessah, H, Fan, C & Trang, T (2017) Animal models of chronic pain: advances and challenges for clinical translation. J Neurosci Res 95, 1242–1256.CrossRefGoogle ScholarPubMed
Klinck, MP, Mogil, JS, Moreau, M, et al. (2017) Translational pain assessment: could natural animal models be the missing link? Pain 158, 1633–1646.CrossRefGoogle ScholarPubMed
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