Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0036572 (seizures)
80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxidative/antioxidative status was investigated in maximal electroshock-induced seizures in mice, a well established model of generalized seizures in humans. Mice were given a single electroshock resulting in tonic convulsions. Total antioxidant capacity (TAC), lipid peroxidation intensity and glutathione peroxidase (GSH-Px) activity was measured spectrophotometrically in the brain, plasma and erythrocytes collected from mice sacrificed at different time points after stimulation. For comparison, sham-stimulated and subeffectively stimulated (no tonic seizures) mice were used. Tonic seizures caused an immediate increase in GSH-Px activity in the brain and during the following three hours the enzyme activity decreased below control values. Similar changes were seen after subconvulsive stimulations, however, a significant increase occurred only one hour after electroshock. A marked TAC reduction in the brain was observed three hours after subconvulsive stimulations. Nevertheless, no significant changes in TAC after tonic seizures were noted. TAC in plasma was significantly reduced three hours after both subconvulsive and convulsive stimulation. Marked reduction of lipid peroxidation intensity in the brain and plasma was recorded after both modes of stimulation. In conclusion, pronounced changes in oxidative/antioxidative status in mice following electroshock are caused by both convulsive and subconvulsive stimuli. Participation of oxidative stress in seizures and pathophysiology of epilepsy awaits further clarification.
...
PMID:Maximal electroshock induces changes in some markers of oxidative stress in mice. 1772 96

Brain preconditioning refers to a wide range of treatments that induce a neuronal tolerance state where neuronal tissue become more resistant to a subsequent lethal insult. The mechanisms underlying the preconditioning-induced brain tolerance are not fully understood, but up-regulation of antioxidant enzymes activity has been suggested to play an important role. In order to test this hypothesis, evaluation of glutathione (GSH) scavenger system was carried out in mice showing the neuroprotective effect of NMDA preconditioning against quinolinic acid (QA)-induced seizures. NMDA is known to prevent seizures in 53% of the animals and completely prevent neural damage against QA. Mice were preconditioned by a non-convulsant NMDA dose (75 mg/kg, 10 ml/kg i.p.) 24 h before QA infusion (4 microl, 9.2 mM i.c.v.). GSH content and enzymatic activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) were evaluated in the cerebral cortex and hippocampus 24 h after QA infusion. NMDA preconditioning and QA infusion did not alter GSH content, GR and G6PDH activities, however, an increase in GST activity was observed in the cerebral cortex from mice. Moreover, NMDA pretreatment was able to prevent the QA-induced decrease in hippocampal GPx activity, but it was not effective against the decreased cortical GPx activity. These results indicate that, although NMDA preconditioning and QA toxicity modulate the activity of some GSH related enzymes, GSH metabolism is not directly linked to the neuroprotective effect induced by NMDA preconditioning.
...
PMID:Evaluation of glutathione metabolism in NMDA preconditioning against quinolinic acid-induced seizures in mice cerebral cortex and hippocampus. 1798 Mar 54

Electroconvulsive therapy has been used in the treatment of psychiatric disorders since the 1930s, but little progress has been made in understanding the cellular mechanisms underlying its therapeutic and adverse effects. Electroconvulsive shock (ECS) in animals provides a common experimental model for studying the effects of electroconvulsive therapy in humans. In order to examine the changes of the brain oxidative stress parameters in several brain structures in the early time period after ECS-induced seizures, the levels of lipid peroxidation as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the rat hippocampus, cerebellum, frontal cortex and the pons/medulla region were determined at different time points during the first 24 h after single ECS-induced seizures. In the hippocampus and cerebellum the levels of lipid peroxidation were unchanged, while the SOD and GSH-Px activities were significantly increased. Levels of lipid peroxidation and the activities of SOD and GSH-Px were not statistically changed in the pons/medulla region. Levels of lipid peroxidation in the frontal cortex were significantly higher in comparison to the control group at all time points examined while the SOD and GSH-Px activities were not statistically changed. In conclusion, the results of the present study indicate that single ECS causes the rat brain structure-specific alterations in the levels of lipid peroxidation as well as in the SOD and GSH-Px activities at different time points within the first 24 h after the seizures induction. Oxidative lipid damage was evident only in the frontal cortex, while the hippocampus, cerebellum and the pons/medulla region remained oxidatively unaffected in our experimental conditions.
...
PMID:Oxidative stress parameters in different rat brain structures after electroconvulsive shock-induced seizures. 1820 11

Oxidative stress may contribute to epileptogenicity in genetic models of epilepsy. To address this, we examined the enzymatic activity of cytosolic Cu/Zn superoxide dismutase (SOD-1), mitochondrial Mn superoxide dismutase (SOD-2), and glutathione peroxidase (GPx) in the developing hippocampus of genetically epilepsy-prone rats (GEPR-9s). We also measured changes in the GSH/GSSG ratio, lipid peroxidation, and protein oxidation at post-natal days (PD) 7, 30, and 90, respectively. Compared with control Sprague-Dawley (SD) rats, GEPR-9s showed similar SOD-1 and SOD-2 activity but lower GPx activity. Epilepsy-prone rats also showed lower GSH/GSSG ratios than controls, and more lipid peroxidation (as measured by malondialdehyde levels) and protein oxidation (as measured by carbonyl levels). Treatment with kainic acid (KA) resulted in more pronounced seizures, less GPx activity, and lower GSH/GSSG ratios in GEPR-9s than in controls, but KA did not significantly affect SOD-1 or SOD-2 activity, suggesting that GEPR-9s do not compensate for reduced GPx activity by increasing SOD. Moreover, KA treatment resulted in significantly a lower GSH/GSSG ratio and GPx-like immunoreactivity and higher malondialdehyde and carbonyl levels in GEPR-9s than in controls. These findings were more evident in GEPR-9s at PD 90 than at PD 30, indicating that oxidative stress is age-dependent. Double-labeling immunocytochemical analysis demonstrated co-localization of GPx-immunoreactive glia-like cells and reactive astrocytes, as labeled by glial fibrillary acidic protein (GFAP). This suggests that mobilization of astroglial cells for synthesis of GPx protein is a response to KA insult, intended to decrease the neurotoxicity induced by peroxides. These responses were more pronounced in control SD rats than in GEPR-9s. Our results suggest that impairment of the GPx (including glutathione)-mediated antioxidant system contributed to epileptogenesis in GEPR-9s.
...
PMID:Role of glutathione peroxidase in the ontogeny of hippocampal oxidative stress and kainate seizure sensitivity in the genetically epilepsy-prone rats. 1822 27

The neuronal ceroidlipofuscinoses (NCL) are a group of neurodegenerative disorders and are the most common lysosomal storage diseases of infancy and childhood. Juvenile NCL is caused by CLN3 mutation, producing retinal degeneration, uncontrollable seizures, cognitive and motor decline, and early death before the age of 30 years. To study the pathogenetic mechanisms of the disease, Cln3 knock-in mice (Cln3(Deltaex7/8)) have been generated, which reproduce the 1.02-kb deletion in the CLN3 gene observed in more than 85% of juvenile NCL patients. To characterize the impact of the common Cln3 mutation on development of autofluorescent storage material, gliosis, glucose metabolism, oxidative stress, and transmitter receptors during postnatal brain maturation, brain tissue of Cln3(Deltaex7/8) mice at the ages of 3, 4, 5, 6, 9, and 19 months was subjected to immunocytochemistry to label gliotic markers and nitric oxide synthases; photometric assays to assess enzyme activities of glycolysis and antioxidative defense systems; and level of reactive nitrogen species as well as quantitative receptor autoradiography to detect select cholinergic, glutamatergic, and GABAergic receptor subtypes. The developmental increase in cerebral cortical autofluorescent lipofuscin-like deposition is accompanied by a significant astro- and microgliosis, increased activities of lactate dehydrogenase and phosphofructokinase, decreased level of glutathione peroxidase, enhanced amount of reactive nitrogen species, and lowered binding levels of N-methyl-D-aspartate- and M1-muscarinic acetylcholine receptors in select brain regions but hardly in GABA(A) receptor sites compared with wild-type mice. Detailed elucidation of the sequence of pathological events during postnatal development highlights new potential strategies for symptomatic treatment of the disease.
...
PMID:Developmental impairments of select neurotransmitter systems in brains of Cln3(Deltaex7/8) knock-in mice, an animal model of juvenile neuronal ceroid lipofuscinosis. 1826 13

A series of N(4)-(naphtha[1,2-d]thiazol-2-yl)semicarbazides were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure tests and minimal motor impairment was determined by rotorod test. A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. Some of the selected compounds were evaluated orally in rats for activity in scPTZ test at several time points (50 mg/kg). The most active compounds carry bromo, fluoro and nitro substituents at 4-position in the phenyl ring. The biochemical estimations of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) from brain homogenate not only clearly implicated the role of free radicals in PTZ-induced convulsion but also explained the possible mechanism of protective effect of semicarbazides, through the reduced formation of MDA and increased formation of SOD and GSH-Px.
...
PMID:Synthesis of some novel N4-(naphtha[1,2-d]thiazol-2-yl)semicarbazides as potential anticonvulsants. 1839 52

The possible neuroprotective effect of progesterone, a steroid hormone, on acute phase changes in a mouse model of cerebral ischaemia induced by bilateral common carotid artery occlusion (BCAO) was studied. A total of 72 male mice were included in the study. The BCAO model was used to induce partial global cerebral ischaemia. Morphological assessment included measurement of infarct size and brain oedema. Post-ischaemic seizure susceptibility was assessed using a subconvulsive dose of pentylenetetrazole (30 mgkg(-1) i.p.). Biochemical estimations included tumour necrosis factor alpha (TNF-alpha) levels and enzyme parameters such as lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase, and protein estimation. BCAO induced a significant infarct size and oedema in the saline-treated control group, along with an increase in oxidative stress, indicated by increased lipid peroxidation and decreased levels of antioxidants such as superoxide dismutase, catalase and glutathione peroxidase. Progesterone (15 mgkg(-1) i.p.) administration showed a neuro-protective effect by significantly reducing the cerebral infarct size as compared with the control group. Post-ischaemic seizure susceptibility was also reduced as the number of positive responders decreased. Brain oedema subsided, but not significantly. Progesterone significantly reduced TNF-alpha levels compared with the ischaemia group. Progesterone improved levels of all the antioxidants, indicating activity against oxidative stress induced by BCAO. The results demonstrate the neuroprotective effect of progesterone against ischaemic insult, suggesting a role for the steroid as a neuroprotective agent.
...
PMID:Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice. 1849 9

To evaluate oxidant status in children after febrile seizures, 61 children were studied: 31 with and 30 without a febrile seizure. Erythrocyte malondialdehyde, glutathione peroxidase, and superoxide dismutase levels were assessed in all patients. Erythrocyte malondialdehyde and glutathione peroxidase levels were significantly higher and superoxide dismutase levels were significantly lower in the febrile seizure group. Febrile seizures may cause significant oxidative stress, and these changes in oxidant status may be a step along the way to cell damage subsequent to febrile seizures.
...
PMID:Oxidant status in children after febrile seizures. 1906 54

N-acetylaspartic acid (NAA) is the biochemical hallmark of Canavan Disease, an inherited metabolic disease caused by deficiency of aspartoacylase activity. NAA is an immediate precursor for the enzyme-mediated biosynthesis of N-acetylaspartylglutamic acid (NAAG), whose concentration is also increased in urine and cerebrospinal fluid of patients affected by CD. This neurodegenerative disorder is clinically characterized by severe mental retardation, hypotonia and macrocephaly, and generalized tonic and clonic type seizures. Considering that the mechanisms of brain damage in this disease remain not fully understood, in the present study we investigated whether intracerebroventricular administration of NAA or NAAG elicits oxidative stress in cerebral cortex of 30-day-old rats. NAA significantly reduced total radical-trapping antioxidant potential, catalase and glucose 6-phosphate dehydrogenase activities, whereas protein carbonyl content and superoxide dismutase activity were significantly enhanced. Lipid peroxidation indices and glutathione peroxidase activity were not affected by NAA. In contrast, NAAG did not alter any of the oxidative stress parameters tested. Our results indicate that intracerebroventricular administration of NAA impairs antioxidant defenses and induces oxidative damage to proteins, which could be involved in the neurotoxicity of NAA accumulation in CD patients.
...
PMID:Intracerebroventricular administration of N-acetylaspartic acid impairs antioxidant defenses and promotes protein oxidation in cerebral cortex of rats. 1929 97

gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound in the central nervous system (CNS) whose tissue concentration are highly increased in the neurometabolic-inherited deficiency of succinic semialdehyde dehydrogenase (SSADH) activity or due to intoxication. SSADH deficiency is biochemically characterized by increased concentrations of GHB in tissues, cerebrospinal fluid, blood and urine of affected patients. Clinical manifestations are variable and include retardation of mental, motor, and language development along with other neurological symptoms, such as hypotonia, ataxia and seizures, whose underlying mechanisms are practically unknown. The precursor of GHB, 1,4-butanediol (1,4-BD) has been used to study the mechanisms of in vivo GHB neurotoxicity. Therefore, in the present work, the effect of acute administration of 20 or 120 mg/Kg 1,4-BD was investigated on various parameters of oxidative stress, such as spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total antioxidant reactivity (TAR), sulfhydryl and protein carbonyl contents, as well as the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in homogenates from cerebral cortex of 14-day-old Wistar rats. Acute administration of 120 mg/Kg 1,4-BD significantly increased spontaneous chemiluminescence and TBA-RS levels, while TAR measurement was markedly diminished, whereas injection of a lower dose (20 mg/Kg) did not change the parameters examined. Other parameters of oxidative stress evaluated were not affected by administration of 1,4-BD. These results indicate that 1,4-BD induces in vivo oxidative stress by stimulating lipid peroxidation and decreasing the non-enzymatic antioxidant defenses in cerebral cortex of young rats. If these effects also occur in humans, it is possible that they might contribute to the brain damage found in SSADH-deficient patients and possibly in individuals intoxicated by GHB or its prodrugs (gamma-butyrolactone or 1,4-BD).
...
PMID:Effects of 1,4-butanediol administration on oxidative stress in rat brain: study of the neurotoxicity of gamma-hydroxybutyric acid in vivo. 1929 10


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---