Oxidative stress in status epilepticus: A clinical-radiological correlation

Kalita, Jayantee; Misra, Usha Kant; Singh, Laxmi Shankar; Tiwari, Anuradha

doi:10.1016/j.brainres.2018.09.038

Cited by 18 publications

(12 citation statements)

References 38 publications

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“…A further recent study has indicated that patients with status epilepticus have reduced antioxidants and increased reactive oxygen and nitrogen species. Furthermore, the study also showed that catalase glutathione and total antioxidant capacity were lower and malondialdehyde and nitric oxide levels were significantly higher in the status epilepticus patients with comorbidity [31]. Moreover, in progressive myoclonic epilepsy, there is considerable evidence that ROS production is a key component of the pathophysiology [32].…”

Section: Ros As a Pathogenic Mechanism In Status Epilepticus And Excimentioning

confidence: 87%

Reactive oxygen species in status epilepticus

Shekh‐Ahmad

Kovač

Abramov

et al. 2019

Epilepsy & Behavior

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There has been growing evidence for a critical role of oxidative stress in neurodegenerative disease, providing novel targets for disease modifying treatments. Although antioxidants have been suggested and tried in the treatment of epilepsy, it is only recently that the pivotal role of oxidative stress in the pathophysiology of status epilepticus has been recognised. Although conventionally thought to be generated by mitochondria, reactive oxygen species during status epilepticus and prolonged seizure are generated activity mainly by NADPH oxidase (stimulated by NMDA receptor activation). Excessive production of reactive oxygen species results in lipid peroxidation, DNA damage, enzyme inhibition and mitochondrial damage, culminating in neuronal death. Antioxidant therapy has been hampered by poor CNS penetration and rapid consumption by antioxidants. However, alternative approaches such as inhibiting NADPH oxidase or increasing endogenous antioxidant defences through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) could avoid these problems. Small molecules that increase Nrf2 activation have proven to be not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. There are a range of Nrf2 activators that are in clinical trial for other indications, suggesting that repurposing of these therapies could provide a rapid translation of these for the treatment of status epilepticus. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

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Section: Ros As a Pathogenic Mechanism In Status Epilepticus And Excimentioning

confidence: 87%

Reactive oxygen species in status epilepticus

Shekh‐Ahmad

Kovač

Abramov

et al. 2019

Epilepsy & Behavior

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“…Oxidative stress, glutamate-mediated excitotoxicity and neuroinflammation underlie the neurobiology of epilepsy, leading to seizure-induced cell death, increased susceptibility to neuronal synchronization, and progressive degeneration of brain areas [ 1 , 2 , 3 , 4 ]. Oxidative stress markers are increased in patients with status epilepticus (SE), correlating with severity, brain MRI, and outcome [ 1 , 2 , 5 , 6 ]. Moreover, targeting oxidative stress prevented epileptogenesis and protected against the cognitive patients decline [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Oxidative stress markers are increased in patients with status epilepticus (SE), correlating with severity, brain MRI, and outcome [ 1 , 2 , 5 , 6 ]. Moreover, targeting oxidative stress prevented epileptogenesis and protected against the cognitive patients decline [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Imbalance of Systemic Redox Biomarkers in Children with Epilepsy: Role of Ferroptosis

et al. 2021

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To assess if ferroptosis, a new type of programmed cell death accompanied by iron accumulation, lipid peroxidation, and glutathione depletion, occurs in children with epilepsy, and in order to identify a panel of biomarkers useful for patient stratification and innovative-targeted therapies, we measured ferroptosis biomarkers in blood from 83 unrelated children with a clinical diagnosis of epilepsy and 44 age-matched controls. We found a marked dysregulation of three ferroptosis key markers: a consistent increase of 4-hydroxy-2-nonenal (4-HNE), the main by-product of lipid peroxidation, a significant decrease of glutathione (GSH) levels, and a partial inactivation of the enzyme glutathione peroxidase 4 (GPX4), the mediator of lipid peroxides detoxification. Furthermore, we found a significant increase of NAPDH oxidase 2 (NOX2) in the blood of children, supporting this enzyme as a primary source of reactive oxygen species (ROS) in epilepsy. Additionally, since the nuclear factor erythroid 2-related factor 2 (NRF2) induction protects the brain from epileptic seizure damage, we also evaluated the NRF2 expression in the blood of children. The antioxidant and anti-inflammatory transcription factor was activated in patients, although not enough to re-establish a correct redox homeostasis for counteracting ferroptosis. Ferroptosis-mediated oxidative damage has been proposed as an emergent mechanism underlying the pathogenesis of epilepsy. Overall, our study confirms a crucial role for ferroptosis in epilepsy, leading to the identification of a panel of biomarkers useful to find new therapeutic targets. Developing innovative drugs, which act by inhibiting the ferroptosis signaling axis, may represent a promising strategy for new anti-seizure medications.

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“…Expanding on these findings, a recently published study confirmed that patients with SE had reduced antioxidants and increased reactive oxygen and nitrogen species. Furthermore, the study also showed that CAT, GSH, and TAC were lower in the SE patients with comorbidity [ 174 ].…”

Section: Quantification Of Oxidative Stress In Clinical Samplesmentioning

confidence: 99%

Approaches for Reactive Oxygen Species and Oxidative Stress Quantification in Epilepsy

et al. 2020

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Oxidative stress (OS) and excessive reactive oxygen species (ROS) production have been implicated in many neurological pathologies, including acute seizures and epilepsy. Seizure-induced damage has been demonstrated both in vitro and in several in vivo seizure and epilepsy models by direct determination of ROS, and by measuring indirect markers of OS. In this manuscript, we review the current reliable methods for quantifying ROS-related and OS-related markers in pre-clinical and clinical epilepsy studies. We first provide pieces of evidence for the involvement of different sources of ROS in epilepsy. We then discuss general methods and assays used for the ROS measurements, mainly superoxide anion, hydrogen peroxide, peroxynitrite, and hydroxyl radical in in vitro and in vivo studies. In addition, we discuss the role of these ROS and markers of oxidative injury in acute seizures and epilepsy pre-clinical studies. The indirect detection of secondary products of ROS such as measurements of DNA damage, lipid peroxidation, and protein oxidation will also be discussed. This review also discusses reliable methods for the assessment of ROS, OS markers, and their by-products in epilepsy clinical studies.

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Oxidative stress in status epilepticus: A clinical-radiological correlation

Cited by 18 publications

References 38 publications

Reactive oxygen species in status epilepticus

Reactive oxygen species in status epilepticus

Imbalance of Systemic Redox Biomarkers in Children with Epilepsy: Role of Ferroptosis

Approaches for Reactive Oxygen Species and Oxidative Stress Quantification in Epilepsy

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