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

Injection of ferric chloride (FeCl3) into the left amygdaloid nucleus of the rat produced partial complex seizures. Subsequent repeated apomorphine challenges revealed steady development of behavioral dopaminergic supersensitivity, above that observed in saline-injected controls. The behavioral supersensitivity observed in FeCl3-injected animals was accompanied by increases in 3H-spiroperidol binding in contralateral amygdala, striatum and ipsilateral nucleus accumbens. In contrast, saline-injected controls demonstrated bilateral decreases in 3H-spiroperidol binding in amygdala and striatum. The effects of FeCl3 injection on the behavioral dopaminergic supersensitivity and 3H-spiroperidol binding were eliminated when the anterior commissure was severed.
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PMID:Dopaminergic supersensitivity at distant sites following induced epileptic foci. 640 28

Intracortical injection of iron ions has been used as a model of posttraumatic epilepsy. Oxidation of lipids in neural membranes by reactive oxygen species, especially hydroxyl radicals (OH), is involved in the mechanisms responsible for iron-induced seizures. We examined the scavenging effects of adenosine (Ado) and 2-chloroadenosine (Cl-Ado) on OH radicals and superoxide (O2.-) using an electron spin resonance (ESR) spectrometer, and the occurrence of epileptic discharges in electrocorticogram (ECoG) induced by FeCl3 injection into the sensorimotor cortex of rats. Though DMPO-O2.- spin adducts generated by the hypoxanthine-xanthine oxidase system were not quenched by Ado or Cl-Ado, 5 mM of each showed a quenching effect on DMPO-OH spin adducts (5.3 x 10(16) spins/ml) generated by the Fenton reagent. In ECoG of rats, spike discharges appeared 15-45 min after FeCl3 injection (500 nmol) into the sensorimotor cortex, and polyspikes and/or ictal patterns were observed 70-90 min after the injection. Cl-Ado (1 mg/kg) or Ado (5 mg/kg) injected intraperitoneally 30 min prior to the FeCl3 injection suppressed or delayed the occurrence of epileptic discharges induced by FeCl3. Cl-Ado and Ado may suppress the occurrence of epileptic discharges by scavenging OH and by their anticonvulsant effect.
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PMID:Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy. 759 Mar 96

The anticonvulsant properties of a mixture of non-esterified alpha-linolenic acid and linoleic acid with a ratio of 1:4 (SR-3) were evaluated in four rat models of epileptic seizures: (1) i.p. injection of a single convulsant dose (50 mg/kg or 100 mg/kg) of pentylenetetrazol; (2) repeated subconvulsant doses of pentylenetetrazol; (3) cortical irritation by intraventricular administration of iron chloride (FeCl3); and (4) audiogenic seizure-prone preparation created by repeated pretreatment with p-cresol. Treatment with SR-3 (about 40 mg/kg i.p.) for a period of 3 weeks prior to challenge was found effective in each of these experimental models and caused up to a 22-fold increase in latency to major motor seizures, up to 84% reduction in the number of rats with seizures, and up to a 97% reduction in the duration of seizures. It is postulated that the anticonvulsant effects of SR-3 may be related to its stabilization of neuronal membranes. SR-3 should be evaluated further as a treatment for epilepsy.
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PMID:Essential fatty acid preparation (SR-3) raises the seizure threshold in rats. 791 28

Glial uptake of beta-[14C]alanine (beta-Ala) was studied in male Sprague-Dawley rats after sub-pial iontophoresis of FeCl3 into the right motor strip. Models bearing a 15-day-old scar were selected because of the presence of strongly reactive glia induced by FeCl3. Behavioral seizures were observed by daily visual inspection in one third of the animals. The effects of intraperitoneal (i.p.) injections of DL-alpha-aminoadipic acid (DLaAA), which exerts specific gliotoxicity through glutamine synthetase (GS) inhibition, and of 3-mercaptoproprionic acid (3MP), a potent inhibitor of glutamic acid decarboxylase (GAD: the rate-limiting enzyme in the biosynthesis of gamma-aminobutyric acid [GABA]), were also examined. There was significant enhancement of beta-Ala uptake in the margins of the scars. Further increases of uptake were triggered by 3MP, and there was extensive recruitment of astrocytes within isocortex even at a distance from the edges of the scar. DL-alpha-Aminoadipic acid caused a slight decrease of beta-Ala uptake, which was selectively localized to the scar margins. Seizure activity was unchanged by high i.p. doses of DL alpha AA. Our results strongly suggest that beta-Ala has high affinity for normal and reactive astrocytes, and that the uptake can be significantly enhanced by lowering endogenous GABA levels in abnormal cortical tissues in and around FeCl3-lesions by inhibition of GAD. Enhancement of glial beta-Ala uptake appeared to depend heavily on increased endothelial transport of small neutral amino acids, in a process modulated by perivascular glia. This model of free radical neurotoxicity may help gain more insight into abnormal neuronal-glial interactions caused by lipid peroxidation.
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PMID:beta-alanine uptake is upregulated in FeCl3-induced cortical scars. 884 51

Rats were microinjected with a 100 mM aqueous solution of ferric chloride into the left amygdaloid body. Behavior was observed and depth electroencephalograms were recorded over the 30 days following injection. All of the FeCl3-injected rats developed isolated epileptiform discharges from the ipsilateral amygdala soon after injection. Within 5 days epileptiform discharges were arising as well from the contralateral amygdala and behavioral seizures were observed. These spontaneous seizures occurred in a pattern associated with stage 4 kindling, with rearing and bilateral forelimb clonus. Seizures persisted during the 30 days of the experiment. Recording from chronically implanted depth electrodes showed development of spike discharges, with recurrent seizures arising from amygdalar regions with propagation into both hippocampi. Aqueous iron is known to initiate lipid peroxidation by free radical mechanisms. Our observations suggest that epileptogenesis followed by chronic, spontaneous seizures could be initiated by deposition of iron-containing compounds into limbic structures of the rat.
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PMID:Amygdalar injection of FeCl3 causes spontaneous recurrent seizures. 974 73

The effect of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on electroencephalographic activity (EEG) was studied in the model of chronic focal epilepsy induced by intracortical injection of FeCl3 in the rat. EEG activity was recorded from the epileptogenic focus (ipsilateral and contralateral) in chronic experiments before and after DSP-4 treatment. In some experiments EEG activity was also simultaneously recorded from the cortical epileptogenic focus and locus coeruleus before and after DSP-4 treatment to study the effect of iron-induced seizure activity and of DSP-4 on the locus coeruleus electrical activity. The results showed that DSP-4 aggravated the iron-induced epileptiform activity as well as the locus-coeruleus electrical activity. The data also showed that, induction of epilepsy by FeCl3 is accompanied by enhancement of the locus coeruleus electrical activity. Our study demonstrates that DSP-4 intensifies and modifies the epileptic activity in the iron-induced chronic epilepsy model and that the effects of toxin persist for a longer duration.
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PMID:Electroencephalographic study of the effect of neurotoxin DSP-4 in iron model of chronic focal epilepsy. 1049 19

Intracortical injection of iron salts causes seizures. Oxidation of lipids in neural membranes by reactive oxygen species is involved in the mechanism responsible for iron-induced seizures as a model of posttraumatic epilepsy. In this study, we examined the effect of trimetazidine (TMZ) and deferoxamine (DFO) on lipid peroxidation after cortical injection of 5 microliters of an aqueous solution containing 100 mM of ferric chloride (FeCl3) in rats. Animals were divided into four groups (n = 7 each) and treated as follows: group 1, saline injection into the cortex (control group); group 2, iron injection into the cortex (injury group); group 3, iron injection into the cortex plus TMZ; group 4, iron injection into the cortex plus DFO. The animals were killed 3 h after injections, and the levels of malondialdehyde (MDA), a lipid peroxidation product, and reduced glutathione (GSH) were measured. A significant elevation of MDA was observed in group 2 (P < 0.05). MDA levels were found to be lower in both the TMZ-treated (P < 0.05) and DFO-treated (P < 0.05) groups than in the injury group. Tissue GSH levels were significantly decreased in group 2 (P < 0.05). GSH levels were increased in the TMZ-treated (P < 0.05) and DFO-treated (P < 0.05) groups compared to the injury group. The results of our study suggest that lipid peroxidation is a critical event in iron-induced epilepsy and that treatment with TMZ and DFO is effective in preventing the formation of free radicals and reducing lipoperoxides in brain tissue.
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PMID:Lipid peroxidation and glutathione levels after cortical injection of ferric chloride in rats: effect of trimetazidine and deferoxamine. 1074 80

Epileptiform discharges and behavioral seizures may be the consequences of the presence of either excessive excitation associated with the neurotransmitter glutamate or from inadequate inhibitory effects associated with gamma-aminobutyric acid (GABA). Synaptic effects of these neurotransmitters are terminated by the action of transporter proteins that remove these amino acids from the synaptic cleft. The glial transporters glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1), and the neuronal transporter excitatory amino acids carrier-1 (EAAC-1) limit excitation initiated by synaptic release of glutamate. Transporter proteins GABA transporter-1 (GAT-1) and GABA transporter-3 (GAT-3) remove GABA from synaptic regions. To assess the molecular effects of the antiepileptic drug valproate, albino rats with chronic, spontaneous, recurrent seizures induced by amygdalar injection of FeCl3 were treated for 14 days with either valproic acid or with saline as an injection control. Regions of the hippocampus were assayed for glutamate and GABA transporters by western blot. While epileptogenesis is thought to correlate with the downregulation of GLAST and upregulation of EAAC-1, valproate caused an increase in the quantity of GLAST protein measured in the hippocampus. Valproate treatment decreased GLT-1 in both control and experimental animals in both hippocampi. EAAC-1 was unchanged by valproate treatment. GABA transporters GAT-1 and GAT-3 in the hippocampus were upregulated by FeCl3 injection into the amygdala. However, valproate caused the downregulation of these GABA transporters in both control and experimental animals. Altered molecular regulation of glutamate appears to be critical in the development of sustained, spontaneous limbic seizures. Our data suggest that valproate may have unique mechanisms of action; specifically, it may affect the removal of glutamate by upregulating GLAST and decreasing GABA transport, which could result in increased tissue concentrations of GABA.
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PMID:Molecular regulation of glutamate and GABA transporter proteins by valproic acid in rat hippocampus during epileptogenesis. 1095 23

The present study was carried out to investigate the effect of trans-resveratrol, a potent antioxidant, against FeCl3-induced posttraumatic seizures. Male Wistar rats weighing 200-250 g were implanted with epidural electrodes and allowed to recover After the recording of baseline EEG. FeCl3 (5 microl, 100 mM) was administered intracortically over a period of 5 min and EEG was monitored for 2 h. Subsequently, rats were sacrificed for the estimation of oxidative stress markers, ie., malondialdehyde (MDA) and glutathione in whole brain tissue. A sham group was run parallel with saline (pH adjusted) and similar protocol for EEG recording and estimation of oxidative stress markers was followed FeCl3-treated animals exhibited epileptiform EEG changes thigh amplitude sharp waves of increased frequency and polyspikes) within 15 min, which continued throughout the period of observation. The level of MDA was found to be significantly elevated, whereas insignificant change was observed in the level of glutathione. trans-Resveratrol (20 and 40 mg/kg ip.) administered 30 min before FeCl3 injection delayed the onset of the appearance of epileptiform EEG changes. The brain MDA levels were also significantly reduced in the trans-resveratrol-treated animals as compared to the vehicle-treated FeCl3-injected rats. The findings show the protective effect of trans-resveratrol in the FeCl3-induced seizure model of posttraumatic seizures.
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PMID:Protective effect of resveratrol against intracortical FeCl3-induced model of posttraumatic seizures in rats. 1171 43

The present study was carried out to investigate the effect of melatonin, a potent antioxidant, and phenytoin, a conventional antiepileptic, against FeCl3-induced posttraumatic seizures. Male Wistar rats weighing 200-250 g were implanted with epidural electrodes and allowed to recover. After the recording of baseline EEG, FeCl3 (5 ul, 100 mM) was administered intracortically over a period of 5 min and EEG was monitored for 2 h. Subsequently, rats were sacrificed to estimate oxidative stress, i.e., the amount of malondialdehyde (MDA) in whole brain tissue. A sham group was run parallel with saline (pH adjusted), and a similar protocol for EEG recording and estimation of oxidative stress was followed. FeCl3-treated animals exhibited epileptiform EEG changes (high amplitude sharp waves of increased frequency and polyspikes) within 15 min, which continued throughout the period of observation. MDA levels were found to be significantly elevated as compared to the sham group. Melatonin (50 mg/kg i.p.) administered 30 min before FeCl3 injection delayed the onset of appearance of epileptiform EEG changes, while at a 100 mg/kg dose of there was complete protection, as none of the animal exhibited epileptiform EEG discharge. Brain MDA levels were also significantly reduced in melatonin (50 and 100 mg/kg dose)-treated animals as compared to the vehicle-treated FeCl3-injected rats. In the phenytoin group, all animals showed epileptiform EEG discharge. However, phenytoin at both 50 and 100 mg/kg dose delayed the onset of epileptiform EEG discharge. There were no significant changes in brain MDA levels in the phenytoin-treated group as compared to controls. Melatonin and phenytoin at doses of 100 mg/kg did not show any sign of motor impairment as observed during the rota-rod test. These findings showed a superior protective effect of melatonin over phenytoin in an intracortical FeCl3 model of posttraumatic epilepsy.
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PMID:Effect of melatonin and phenytoin on an intracortical ferric chloride model of posttraumatic seizures in rats. 1208 76


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