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Perinatal and Prenatal Disorders pp 371–394Cite as

Oxidative Stress in Epilepsy

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Abstract

The brain is particularly susceptible to oxidative stress being the most aerobically active organ in the body due to its high metabolic demands. It also contains high concentrations of polyunsaturated fatty acids that are prone to lipid peroxidation and is rich in iron which can catalyze hydroxyl radical formation. There is evidence that neuronal hyperexcitability and oxidative injury produced by an excessive production of free radicals may play a role in the initiation and progression of epilepsy. Epilepsy is one of the most common neurological disorders and may provoke serious physical, psychological, socioeconomic consequences. Understanding the role of oxidative stress in the pathophysiology of seizures is essential to delineate appropriate therapeutic strategies. Compounds with neuroprotective or antioxidant function may exert positive effects when associated with antiepileptic drugs (AEDs). The latter themselves may play a role of antioxidants or neuroprotectants. In fact, most AEDs currently in use have been tested for a possible neuroprotective ability both in human and animal models of epilepsy.

The present review is intended to outline the current state of knowledge on the relationship between oxidative stress and epilepsy. Evidence of damage to lipids, DNA, and proteins as the consequence of seizure-related oxidative stress, occurring in various animal models of epilepsy, is reviewed. The role of compounds with neuroprotective effects in the therapeutic strategy to prevent or treat epilepsy is also discussed.

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Abbreviations

8-dG:

8-2′-deoxyguanosine

8-oxo-dG (8-OH-dG):

8-hydroxy-2′-deoxyguanosine

AEDs:

antiepileptic drugs

ATP:

adenosine triphosphate

BBB:

blood-brain barrier

CBZ:

carbamazepine

CoQ10:

ubiquinone or coenzymeQ10

CSF:

cerebral spinal fluid

Cu/ZnSOD:

copper-zinc SOD

DNA:

deoxyribonucleic acid

F2-Iso-Ps:

F2-isoprostanes

FBM:

felbamate

GABA:

γ-aminobutyric acid

GPx:

glutathione peroxidase

GPx-GR:

glutathione peroxidase-glutathione reductase

GSH:

glutathione tripeptide

H2O2 :

hydrogen peroxide

LEV:

levetiracetam

LMT:

lamotrigine

MLT:

melatonin

MnSOD:

manganese SOD

mtDNA:

mitochondrial DNA

NAC:

N-acetylcysteine

NADH:

nicotinamide adenine dinucleotide (reduced status)

NMDA receptor:

N-methyl-D-aspartate receptor

NO:

nitric oxide

PHT:

phenytoin

POLG1:

mitochondrial DNA polymerase γ

ROS:

reactive oxygen species

SOD:

superoxide dismutase

TPM:

topiramate

tRNAPhe:

phenylalanine transfer RNA

TRPM2:

transient receptor potential M2 channel

TSPO:

translocation protein

VPA:

valproic acid

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Authors and Affiliations

  1. Pediatric Neurology-Immunology and Endocrinology Unit, Department of Pediatrics, Gynecology, Obstetrics, and Reproductive Medicine, University of Siena, Via M. Bracci, Le Scotte, 53100, Siena, Italy

    Salvatore Grosso M.D., Ph.D. & Ursula Geronzi M.D.

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  1. Salvatore Grosso M.D., Ph.D.
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  2. Ursula Geronzi M.D.
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Correspondence to Salvatore Grosso M.D., Ph.D. .

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  1. University of Penn, Perelman Sch of Med Professor of Pediatrics, Children's Hospital of Philadelphia Division of Neonatology, Philadelphia, Pennsylvania, USA

    Phyllis A. Dennery

  2. Lab of Oxidative Stress Policlinico “Le Scotte“, University of Siena Dept of Peds, Obstetrics & Reprod Med, Siena, Italy

    Giuseppe Buonocore

  3. Department of Pediatrics, University of Oslo Faculty of Medicine Rikshospitalit Medical Center, Oslo, Norway

    Ola Didrik Saugstad

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Grosso, S., Geronzi, U. (2014). Oxidative Stress in Epilepsy. In: Dennery, P., Buonocore, G., Saugstad, O. (eds) Perinatal and Prenatal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1405-0_20

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