Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of delta 9-tetrahydrocannabinol (delta 9-THC), two of its metabolites, 8 beta-hydroxy-delta 9-THC and 11-hydroxy-delta 9-THC, and cannabidiol were comparatively studied by means of an iron-induced cortical focal epilepsy in conscious rats with chronically implanted electrodes. delta 9-Tetrahydrocannabinol produced depression of the spontaneously firing epileptic focus, excitatory behavior, generalized after-discharge-like bursts of epileptiform polyspikes and frank convulsions. The pharmacological profiles of the two metabolites differed from that of the parent compound: 11-Hydroxy-delta 9-THC did not precipitate convulsions, but it did elicit all the other effects of delta 9-THC; the 8 beta-hydroxy derivative, on the other hand, exerted only two delta 9-THC-like effects; that is, it evoked polyspike bursts and convulsions. In contrast, cannabidiol, even in large doses (100 mg/kg) was devoid of all the effects of delta 9-THC. Furthermore, pretreatment with cannabidiol markedly altered the responses to delta 9-THC in the following ways: focal depression was partially blocked, polyspike activity was enhanced and convulsions abolished. Phenytoin pretreatment elicited similar effects, but it failed to block the delta 9-THC-induced convulsions. In general, the cannabinoids exhibit a wide spectrum of CNS effects ranging from focal depression to convulsions; specifically, however, the pharmacological profile of each agent can differ markedly; for example, the convulsant properties of delta 9-THC are not a universal characteristic of this class of drugs.
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PMID:Central excitatory properties of delta 9-tetrahydrocannabinol and its metabolites in iron-induced epileptic rats. 627 53

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

An iron induced model of posttraumatic chronic focal epilepsy in rats was studied with respect to extracellular amino acids, electrophysiology, and morphology, approx. 6 months after intracortical injection of ferrous chloride. Twenty-six of the twenty-eight (93%) rats developed spontaneous epileptiform EEG-activity and electrical cortical stimulation done in eight animals evoked seizure activity in five animals (62.5%). Epileptic brain tissue displayed significantly higher extracellular interictal levels of aspartate (ASP), compared to normal brain, measured with intracerebral microdialysis. The interictal levels of serine (SER) were significantly higher at the lesion side compared to the contralateral cortex in epileptic animals. Spontaneous elevations of ASP and glutamate (GLU) levels up to 8 times the basal level were found in 4/5 (80%). There was no consistent amino acid pattern following the electrically induced seizures, but in association with more intense seizure activity ASP and GLU were elevated. Histopathologically, the necrotic lesions in the cortex contained small vessels and iron pigment loaded astrocytes. Scattered eosinophilic neurons were found in the hippocampus, bilaterally in 37% of the animals. The results show that a focal epileptiform activity developed in a high percentage of animals that received an intracortical iron injection. The observed amino acid changes in epileptic animals may be involved in the development of seizures in this model of posttraumatic epilepsy.
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PMID:Extracellular amino acid levels measured with intracerebral microdialysis in the model of posttraumatic epilepsy induced by intracortical iron injection. 1116 2

The iron-induced model of post-traumatic chronic focal epilepsy in rats was studied by depth-electrode mapping to investigate the spread of epileptiform activity into subcortical brain structures after its onset in the cortical epileptic focus. Electrical seizure activity was recorded in the hippocampal CA1 and CA3 areas, amygdala and caudate-putamen, in rats with iron-induced chronic cortical focal epilepsy. These experiments showed that the epileptiform activity with its onset in the cortical focus synchronously propagated into the studied subcortical brain areas. Seizure behaviours seemed to increase in correspondence with the spread of the epileptic electrographic activity in subcortical areas. Comparison of the cortical focus electroencephalographic and associated multiple-unit action potential recordings with those from the subcortical structures showed that the occurrence and evolution of the epileptiform activity in the subcortical structures were in parallel with that in the cortical focus. The intracerebral anatomic progression and delineation of seizure spread (mapped by field potential (EEG) and multiple-unit action potentials (MUA) recordings) indicated participation of these regions in the generalization of seizure activity in this model of epilepsy. The seizure-induced activation of the hippocampus appeared to evolve into an epileptic focus independent of the cortical focus. The present study demonstrates the propagation of epileptic activity from the cortical focus into the limbic and basal ganglia regions. Treatment of iron-induced epileptic rats with ethosuximide, an anti-absence drug, resulted in suppression of the epileptiform activity in the cortical focus as well as in the subcortical brain areas.
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PMID:Iron-induced experimental cortical seizures: electroencephalographic mapping of seizure spread in the subcortical brain areas. 1762 12

A model is a simplified preparation that reproduces only the most critical features of a disease. To be considered as a validated animal model, such an experimental preparation must fulfill three criteria: isomorphism or similarities of the symptoms; predictivity or identical pharmacological reactivity; homology or etiological similarity. In epilepsy, the use of animal models helps our understanding of physiological and pathological networks involved in the genesis, maintenance, and propagation of seizures. The animal models of epilepsy are also useful in designing and testing new surgical therapeutical strategies, in particular using deconnection or neuromodulation in drug-resistant focal epilepsies. Here we describe three animal models of focal epilepsy, adapted to addressing experimental surgery issues. Kindling consists in the regular liminar stimulation of a given brain structure in the rodent to develop a focal discharge that is secondarily generalized. The local application of epileptogenic agents such as cobalt, iron, or penicillin leads to focal discharges that do not generalize in the rodent or the primate. It is a model of focal neocortical epilepsy without secondary generalization. The focal application of kainate, an excitotoxic glutamate agonist, in the dorsal hippocampus of the adult mouse results, after a latent period, in spontaneous and recurrent focal discharges, behavioral interictal troubles, drug resistance, and histological anomalies reminiscent of hippocampal sclerosis. This constitutes a model of mesial-temporal epilepsy. Better knowledge, in these models, of the neural networks generating, propagating, and/or controlling the seizures should make it possible to design innovative surgical approaches for the treatment of drug-resistant epilepsies.
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PMID:[Animal models to develop surgery of focal epilepsies?]. 1841 67

For patients with drug-resistant focal epilepsy, excision of the epileptogenic zone is the most effective treatment approach. However, the surgery is less effective in the 15-30% of patients whose lesions are not distinct when visualized by magnetic resonance imaging (MRI). Here, we show that an intravenously administered MRI contrast agent consisting of a paramagnetic polymer coating encapsulating a superparamagnetic cluster of ultrasmall superparamagnetic iron oxide crosses the blood-brain barrier and improves lesion visualization with high sensitivity and target-to-background ratio. In kainic-acid-induced mouse models of drug-resistant focal epilepsy, electric-field changes in the brain associated with seizures trigger breakdown of the contrast agent, restoring the T1-weighted magnetic resonance signal, which otherwise remains quenched due to the distance-dependent magnetic resonance tuning effect between the cluster and the coating. The electric-field-responsive contrast agent may increase the probability of detecting seizure foci in patients and facilitate the study of brain diseases associated with epilepsy.
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PMID:An electric-field-responsive paramagnetic contrast agent enhances the visualization of epileptic foci in mouse models of drug-resistant epilepsy. 3298 85