Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to explore the relation between the modulation of cerebral blood flow and the latency of hyperbaric oxygen-induced convulsion. There were two parts in this study. First, the effect of acetazolamide on the latency of hyperbaric oxygen-induced convulsion was observed. 32 Sprague-Dawley (SD) rats were randomly divided into four groups: the acetazolamide 200, 20, 2 mg/kg body weight and normal saline (NS) group. The animals were given intraperitoneally acetazolamide or NS, respectively, before being exposed to the pressure of 6 ATA (absolute atmosphere) of pure oxygen. The time from exposure to the onset of seizure (clonic-tonic convulsion) was recorded for each animal according to behavioral observation. Second, the changes in maleic dialdehyde (MDA) and the activity of glutathione peroxidase (GSH-PX) were measured after acetazolamide treatment. 40 SD rats were randomly divided into five groups: NS group, 6 min with NS group, 6 min with acetazolamide group, 16 min with NS group, and 16 min with acetazolamide group. The dose of acetazolamide was 20 mg/kg body weight. After injection of NS or acetazolamide, the animals were subjected to the pressure of 6 ATA of pure oxygen in respect to its time course group. The rats were decapitated and the cortex, hippocampus, and striatum of brains were dissected and homogenized. The content of MDA and the activity of GSH-PX in these tissues were determined. We found that (1) there was a significant difference in the latency of hyperbaric oxygen-induced convulsion between the acetazolamide 200 mg/kg group and the NS control group, as well as between the acetazolamide 20 mg/kg group and the NS control group (P<0.01), whereas there was no significant difference between the NS group and the acetazolamide 2 mg/kg weight group (P>0.05). The latency of these groups were listed as follows: 9.78+/-1.94 min for 200 mg/kg body weight group, 10.92+/-1.68 min for 20 mg/kg body weight group, 24.32+/-4.33 min for 2 mg/kg body weight group and 22.02+/-4.32 min for NS control group. (2) there was no significant difference between all groups in the activity of GSH-PX, though it varied with the oxidation levels. In the cortex and hippocampus, the activity of GSH-PX boosted up at first, but with the progress of the oxidation it was impaired. In the striatum, the activity of GSH-PX increased stepwise with the aggravation of the oxidation. The MDA content in the cortex increased significantly in the group of 6 min with acetazolamide (P<0.01), as well as the group of 16 min with acetazolamide group both in cortex and hippocampus (P<0.01, P<0.05). The MDA content of all groups is correlated with the dose of acetazolamide and the exposure time. These results suggest that acetazolamide which dilates the brain arteriolar obviously shortens the latency of hyperbaric oxygen-induced convulsion, and that acetazolamide dilates the vessels and increases the supply of the oxygen breaking into the brain tissues and aggravates the oxidation. The hyperbaric oxygen-induced convulsion correlates closely with the oxidation injury.
 ...
PMID:[Effect of acetazolamide on the latency of hyperbaric oxygen-induced convulsion]. 1512 24

In the present study we examined the effects of pentylenetetrazol (PTZ) administration on the thiol redox state (TRS), lipid peroxidation and protein oxidation in left and right mouse cerebral cortex in order (a) to quantitate the major components of the thiol redox state and relate them with oxidative stress and cortical laterality, and (b) to investigate whether neuronal activation without synchronization, induced by subconvulsive doses of PTZ, can cause similar qualitative effects on the thiol redox state. Specifically, we examined the TRS components [glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), protein (P) thiols (PSH) and protein and non-protein (NP) mixed/symmetric disulfides (PSSR, NPSSR, NPSSC, PSSP)]. At 15 min after seizure, GSH, GSSG, CSH, NPSSC, PSSR and PSSC levels are decreased in left (14-50%) and right (11-53%) cortex while PSSP levels are increased in both left (1400%) and right (1600%) cortex. At 30 min after seizure, GSSG, CSH, NPSSC, PSSR and PSSC levels are decreased in left (14-51%) and right (18-56%) cortex while PSSP and protein carbonyl levels are increased in left (2300% and 20%, respectively) and right (2800% and 21%, respectively) cortex. At 24 h after seizure, the TRS components return to normal and protein carbonyl levels are decreased in left (16%) and right (20%) cortex. The significant decrease in GSH, GSSG, CSH, NPSSC, PSSR and PSSC, as well as the increase in protein carbonyl and the high increase in PSSP levels after PTZ-induced seizure indicate increased oxidative stress in cerebral cortex of mice, and of similar magnitude and TRS-component profiles between left and right cerebral cortex.
 ...
PMID:Effect of pentylenetetrazol-induced epileptic seizure on thiol redox state in the mouse cerebral cortex. 1551 33

1. Epilepsy is one of the major neurological disorders of the brain, affecting approximately 0.5-1.0% of the population worldwide. Various neurotransmitter abnormalities, especially of GABA and glutamate, have been reported to play a key role in the pathophysiology of epilepsy. 2. Cyclo-oxygenase (COX) is the rate-limiting enzyme in the production of prostaglandins and, as such, is a key target for many anti-inflammatory drugs. Cyclo-oxygenase has been reported to play a significant role in neurodegeneration. Recent studies have reported that COX plays a significant role in the pathophysiology of epilepsy. 3. The aim of the present study was to explore the possible role of COX and the effect of COX inhibitors in epilepsy. 4. Kindling is a chronic model of epilepsy. In the present study, kindling was induced in mice by chronic administration of a subconvulsive dose of pentylenetetrazole (PTZ; 40 mg/kg) on every other day for a period of 15 days. Naproxen was administered daily 45 min before PTZ or vehicle. The kindling score was recorded after PTZ administration. Seizure severity was measured according to a prevalidated scoring scale. Biochemical estimations were performed immediately after recording behavioural parameters on the 16th day of PTZ treatment. 5. Chronic treatment with PTZ significantly induced kindling in mice. Pretreatment with the non-selective COX inhibitor naproxen (7 and 14 mg/kg, i.p.) showed significant protection against PTZ-induced kindling in mice. Biochemical analysis revealed that chronic treatment with PTZ significantly increased lipid peroxidation and nitrite levels (NO levels), but decreased reduced glutathione (GSH) levels in brain homogenates. 6. In conclusion, the results of the present study strongly suggest that COX plays an important role in the pathophysiology of PTZ-induced kindling in mice and that COX inhibitors could be a useful neuroprotective strategy for the treatment of epilepsy.
 ...
PMID:Effect of naproxen, a non-selective cyclo-oxygenase inhibitor, on pentylenetetrazol-induced kindling in mice. 1602 18

The time course and critical determinants of mitochondrial dysfunction and oxidative stress following limbic status epilepticus (SE) were investigated in hippocampal sub-regions of an electrical stimulation model in rats, at time points 4-44h after status. Mitochondrial and cytosolic enzyme activities were measured spectrophotometrically, and reduced glutathione (GSH) concentrations by HPLC, and compared to results from sham controls. The earliest change in any sub-region was a fall in GSH, appearing as early as 4h in CA3 (-13%, p<0.05), and persisting at all time points. This was followed by a transient fall in complex I activity (CA3, 16h, -13%, p<0.05), and later changes in aconitase (CA1,-18% and CA3, -22% at 44h, p<0.05). The activity of the cytosolic enzyme glyceraldehyde-3-phosphate-dehydrogenase was unaffected at all time points. It is known that GSH levels are dependent both on redox status, and on the availability of the precursor cysteine, in turn dependent on the cysteine/glutamate antiporter, for which extracellular glutamate concentrations are rate limiting. Both mechanisms are likely to contribute indirectly to GSH depletion following seizures. That a relative deficiency in GSH precedes later changes in the activities of complex I and aconitase in vulnerable hippocampal sub-regions, occurring within a clinically relevant therapeutic time window, suggests that strategies to boost GSH levels and/or otherwise reduce oxidative stress following seizures, deserve further study, both in terms of preventing the biochemical consequences of SE and the neuronal dysfunction and clinical consequences.
 ...
PMID:Depletion of reduced glutathione precedes inactivation of mitochondrial enzymes following limbic status epilepticus in the rat hippocampus. 1629 Mar 21

The aim of this study was to determine seizure-induced oxidative stress by measuring hippocampal glutathione (GSH) and glutathione disulfide (GSSG) levels in tissue and mitochondria. Kainate-induced status epilepticus (SE) in rats resulted in a time-dependent decrease of GSH/GSSG ratios in both hippocampal tissue and mitochondria. However, changes in GSH/GSSG ratios were more dramatic in the mitochondrial fractions compared to hippocampal tissue. This was accompanied by a mild increase in glutathione peroxidase activity and a decrease in glutathione reductase activity in hippocampal tissue and mitochondria, respectively. Since coenzyme A (CoASH) and its disulfide with GSH (CoASSG) are primarily compartmentalized within mitochondria, their measurement in tissue was undertaken to overcome problems associated with GSH/GSSG measurement following subcellular fractionation. Hippocampal tissue CoASH/CoASSG ratios were decreased following kainate-induced SE, the time course and magnitude of change paralleling mitochondrial GSH/GSSG levels. Cysteine, a rate-limiting precursor of glutathione was decreased following kainate administration in both hippocampal tissue and mitochondrial fractions. Together these changes in altered redox status provide further evidence for seizure-induced mitochondrial oxidative stress.
 ...
PMID:Seizure-induced changes in mitochondrial redox status. 1641 13

A-type K+ channels are crucial determinants of neuronal firing. For example, reducing the amplitude of A-type currents (I(A)) increases seizure susceptibility. We have therefore examined the functional and molecular properties of I(A) in dentate granule neurons following pilocarpine-induced status epilepticus (SE). We found that the levels of various A-type channel subunit mRNAs are unaltered following SE. Furthermore, current density and biophysical properties of I(A) recorded in outside-out and cell-attached patches from dentate granule cells are not modified by SE. However, I(A) in both control and epileptic rats was powerfully regulated by the cellular redox state. I(A) was recorded in outside-out patches with the recording pipette containing either reduced (GSH) or oxidized (GSSG) glutathione. In both control and epileptic rats, the presence of GSSG caused a similar, marked acceleration of recovery from inactivation. Additionally, GSSG produced a small but significant reduction of I(A) amplitudes only in control rats. The inactivation time course of I(A) during depolarizing voltage steps was not modified by GSH or GSSG. Cell-attached recordings, in which the intracellular milieu is conserved, revealed a slow time course of recovery more comparable to that with GSH. In summary, epileptic activity does not produce chronic changes in the molecular and functional properties of the somatic I(A) of dentate granule cells. However, I(A) is powerfully modulated by oxidation in both control and epileptic rats. This finding suggests that the availability of I(A) may be strongly regulated by changes in the GSH/GSSG ratio occurring during prolonged seizure activity or hypoxia.
 ...
PMID:Functional properties and oxidative modulation of A-type K currents in hippocampal granule cells of control and chronically epileptic rats. 1648 49

In view of a role of oxidative stress in epilepsy and the evidence for the involvement of peroxidative injury in sodium valproate (SVP)-induced adverse effects on liver and kidneys, we investigated whether the combination of SVP with N-acetylcysteine (NAC), an antioxidant, may help us to achieve maximal efficacy in terms of seizure control, with minimal toxicity on liver and kidneys. Pentylenetetrazole (PTZ)-induced seizures were used to evaluate the anticonvulsant effect of drugs. Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in brain tissue and glutathione (GSH) levels in liver and kidney tissues. Aspartate aminotransferase and alanine aminotransferase concentrations in the serum were also determined to assess liver function. In our study, NAC exhibited a nondose-dependent anticonvulsant effect. The concurrent administration of NAC with SVP significantly prolonged the latency to jerks, myoclonus and clonic generalized seizures. No significant oxidative stress was evident in brain tissue following PTZ-induced seizures, though an elevation of serum transaminase enzymes was seen. SVP at the dose studied did not produce any significant oxidative stress on the liver and kidneys, while treatment with NAC elevated liver and kidney GSH levels. The concurrent administration of NAC with SVP had beneficial effects on liver and kidney cells.
 ...
PMID:Modulation of pentylenetetrazole-induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N-acetylcysteine. 1667 59

: Oxidative stress has been implicated in a large number of human degenerative diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent with broad-spectrum effects on seizures and animal models of epilepsy. Recently, it was demonstrated that the mechanism of LEV differs from that of conventional antiepileptic drugs. Objectifying to investigate if LEV mechanism of action involves antioxidant properties, lipid peroxidation levels, nitrite-nitrate formation, catalase activity, and glutathione (GSH) content were measured in adult mice brain. The neurochemical analyses were carried out in hippocampus of animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg, s.c. (P400) produced a significant increase of lipid peroxidation level in hippocampus. LEV pretreatment was able to counteract this increase, preserving the lipid peroxidation level in normal value. P400 administration also produced increase in the nitrite-nitrate formation and catalase activity in hippocampus, beyond a decrease in GSH levels. LEV administration before P400 prevented the P400-induced alteration in nitrite-nitrate levels and preserved normal values of catalase activity in hippocampus. Moreover, LEV administration prevented the P400-induced loss of GSH in this cerebral area. The present data suggest that the protective effects of LEV against pilocarpine-induced seizures can be mediated, at least in part, by reduction of lipid peroxidation and hippocampal oxidative stress.
 ...
PMID:Effects of levetiracetam in lipid peroxidation level, nitrite-nitrate formation and antioxidant enzymatic activity in mice brain after pilocarpine-induced seizures. 1720 90

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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>