Role of oxidative stress in epileptic seizures
TL;DR: This review highlights pharmacological mechanisms associated with oxidative stress in epileptic seizures and the potential for neuroprotection in epilepsy that targets oxidative stress and is supported by effective antioxidant treatment.
About: This article is published in Neurochemistry International.The article was published on 2011-08-01 and is currently open access. It has received 340 citations till now. The article focuses on the topics: Epilepsy & Neuroprotection.
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TL;DR: There is evidence that suggests that antioxidant therapy may reduce lesions induced by oxidative free radicals in some animal seizure models, and few studies have shown an established link between oxidative stress, seizures, and age.
Abstract: Backgrounds. The production of free radicals has a role in the regulation of biological function, cellular damage, and the pathogenesis of central nervous system conditions. Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. Experimental studies suggest that oxidative stress is a contributing factor to the onset and evolution of epilepsy. Objective. A review was conducted to investigate the link between oxidative stress and seizures, and oxidative stress and age as risk factors for epilepsy. The role of oxidative stress in seizure induction and propagation is also discussed. Results/Conclusions. Oxidative stress and mitochondrial dysfunction are involved in neuronal death and seizures. There is evidence that suggests that antioxidant therapy may reduce lesions induced by oxidative free radicals in some animal seizure models. Studies have demonstrated that mitochondrial dysfunction is associated with chronic oxidative stress and may have an essential role in the epileptogenesis process; however, few studies have shown an established link between oxidative stress, seizures, and age.
217 citations
Cites background from "Role of oxidative stress in epilept..."
...Therefore in the KA induction model there is an increase in ROS production, mitochondrial dysfunction, and apoptosis of neurons in several areas of the brain, especially those in the hippocampus [72]....
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TL;DR: Evidence is summarized that suggest what is the role of oxidative stress on induction of apoptosis in experimental models of epilepsy and how this affects bioenergetics state failure and impaired mitochondrial function.
Abstract: Epilepsy is considered one of the most common neurological disorders worldwide. Oxidative stress produced by free radicals may play a role in the initiation and progression of epilepsy; the changes in the mitochondrial and the oxidative stress state can lead mechanism associated with neuronal death pathway. Bioenergetics state failure and impaired mitochondrial function include excessive free radical production with impaired synthesis of antioxidants. This review summarizes evidence that suggest what is the role of oxidative stress on induction of apoptosis in experimental models of epilepsy.
170 citations
Cites background from "Role of oxidative stress in epilept..."
...Excessive ROS generation can cause damage of neuronal cells inducing cell death via either an apoptotic or a necrotic pathway [13]....
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TL;DR: The data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy are reviewed.
Abstract: An insult to the brain (such as the first seizure) causes excitotoxicity, neuroinflammation, and production of reactive oxygen/nitrogen species (ROS/RNS). ROS and RNS produced during status epilepticus (SE) overwhelm the mitochondrial natural antioxidant defense mechanism. This leads to mitochondrial dysfunction and damage to the mitochondrial DNA. This in turn affects synthesis of various enzyme complexes that are involved in electron transport chain. Resultant effects that occur during epileptogenesis include lipid peroxidation, reactive gliosis, hippocampal neurodegeneration, reorganization of neural networks, and hypersynchronicity. These factors predispose the brain to spontaneous recurrent seizures (SRS), which ultimately establish into temporal lobe epilepsy (TLE). This review discusses some of these issues. Though antiepileptic drugs (AEDs) are beneficial to control/suppress seizures, their long term usage has been shown to increase ROS/RNS in animal models and human patients. In established TLE, ROS/RNS are shown to be harmful as they can increase the susceptibility to SRS. Further, in this paper, we review briefly the data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy.
166 citations
Cites background from "Role of oxidative stress in epilept..."
...During latent period, nitrosylation of protein fragments and posttranslational modifications of ion channels and transporters will further lead to hyperexcitability of neurons [24, 48, 82, 83, 85, 86]....
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TL;DR: The essential trace element selenium, as selenocysteine, is incorporated into antioxidant selenoproteins such as glutathione peroxidases, thioredoxin reductases and Sepp1 and taken up by neurons via the apolipoprotein E receptor 2 (ApoER2).
162 citations
TL;DR: The present review's findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy.
150 citations
References
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TL;DR: When hemolyzates from erythrocytes of selenium-deficient rats were incubated in vitro in the presence of ascorbate or H2O2, added glutathione failed to protect the hemoglobin from oxidative damage.
Abstract: When hemolyzates from erythrocytes of selenium-deficient rats were incubated in vitro in the presence of ascorbate or H(2)O(2), added glutathione failed to protect the hemoglobin from oxidative damage. This occurred because the erythrocytes were practically devoid of glutathione-peroxidase activity. Extensively purified preparations of glutathione peroxidase contained a large part of the (75)Se of erythrocytes labeled in vivo. Many of the nutritional effects of selenium can be explained by its role in glutathione peroxidase.
6,893 citations
"Role of oxidative stress in epilept..." refers background in this paper
...Since 1973, when Rotruck et al. revealed the role of Se in the detoxifying enzyme GPx, this element has been shown to have a positive biological function in various aspects of human health (Rotruck et al., 1973; Rayman, 2000)....
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TL;DR: Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.
Abstract: BACKGROUND: More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. METHODS: We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. RESULTS: Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). CONCLUSIONS: Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.
4,326 citations
TL;DR: Two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain.
Abstract: There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.
3,844 citations
"Role of oxidative stress in epilept..." refers background in this paper
...Oxidative stress and excessive glutamate receptor activation represent sequential, as well as interacting, factors that converge as a final common pathway for neuronal vulnerability (Coyle and Puttfarcken, 1993)....
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TL;DR: It is shown that micromolar concentrations of H2O2 can induce the expression and replication of HIV‐1 in a human T cell line and suggests that diverse agents thought to activate NF‐kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI.
Abstract: Hydrogen peroxide and oxygen radicals are agents commonly produced during inflammatory processes. In this study, we show that micromolar concentrations of H2O2 can induce the expression and replication of HIV-1 in a human T cell line. The effect is mediated by the NF-kappa B transcription factor which is potently and rapidly activated by an H2O2 treatment of cells from its inactive cytoplasmic form. N-acetyl-L-cysteine (NAC), a well characterized antioxidant which counteracts the effects of reactive oxygen intermediates (ROI) in living cells, prevented the activation of NF-kappa B by H2O2. NAC and other thiol compounds also blocked the activation of NF-kappa B by cycloheximide, double-stranded RNA, calcium ionophore, TNF-alpha, active phorbol ester, interleukin-1, lipopolysaccharide and lectin. This suggests that diverse agents thought to activate NF-kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI. ROI appear to serve as messengers mediating directly or indirectly the release of the inhibitory subunit I kappa B from NF-kappa B.
3,793 citations
"Role of oxidative stress in epilept..." refers background in this paper
...The dissociation can be triggered by oxygen free radicals, among other factors, (Schreck et al., 1991), and NF-jB is widely viewed as an oxidative stress-responsive factor....
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...The dissociation can be triggered by oxygen free radicals, among other factors, (Schreck et al., 1991),...
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TL;DR: Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.
3,359 citations
"Role of oxidative stress in epilept..." refers background in this paper
...Since 1973, when Rotruck et al. revealed the role of Se in the detoxifying enzyme GPx, this element has been shown to have a positive biological function in various aspects of human health (Rotruck et al., 1973; Rayman, 2000)....
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