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

In our previous studies, we hypothesized that activation and subsequent collapse of GABA-mediated inhibition during tetanus is an important seizure-triggering mechanism in the kindled epileptogenic focus. To examine this hypothesis, in the present study, we investigated the effects of pharmacological manipulations of the kindled amygdala with several drugs, and measured the kindled seizures as well as the EEG events during tetanus. The results obtained were: (i) The selective GABA-A agonist, muscimol (1 and 5 nM/1 microliter), suppressed kindled seizures in a dose-dependent fashion, and the 5 nM muscimol significantly prolonged EEG suppression and reduced the number of oscillations in the subsequent rhythmic synchronous discharge. Similar effects followed systemic injection of diazepam (2 mg/kg). (ii) The selective GABA-B agonist, baclofen (5 nM), had no effect on kindled seizures nor on the EEG events during tetanus. (iii) The NMDA antagonist, 2-amino-5-phosphonovaleric acid (80 nM), significantly reduced the afterdischarge duration and significantly delayed the appearance of the rhythmic synchronous discharge. However, these effects were not observed immediately, but 24 to 72 h after microinjection. (iv) The muscarinic cholinergic antagonist, atropine (40 and 80 nM), suppressed kindled seizures in a dose-dependent fashion, but the atropine caused marked synchronous discharge both in the awake resting EEG and during tetanic stimulation. We conclude that the GABA-A system, including the benzodiazepine system, is more involved in the seizure-triggering mechanism of amygdala kindling than the GABA-B system, that there is an interaction between the GABA-A and NMDA system, and that the cholinergic participation is independent of the primary seizure-triggering mechanisms.
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PMID:Kindling-induced changes in EEG recorded during stimulation from the site of stimulation. III. Direct pharmacological manipulations of the kindled amygdala. 288 27

Strychnine poisoning leads to seizures that have traditionally been attributed to competitive antagonism of glycine receptors in the spinal cord. Although glycine is thought to act as an inhibitory neurotransmitter, a strychnine-insensitive glycine (Gly2) receptor has been recently described in cultured mouse neurons that is thought to be allosterically linked to the excitatory amino acid NMDA receptor. The present study demonstrates that intrathecally administered glycine, in contrast to other putative inhibitory transmitters, potentiates rather than inhibits strychnine-induced convulsions in mice. The seizure-potentiating effects of glycine are blocked by aminophosphonovaleric acid, an NMDA antagonist. In addition, in animals pretreated with a subconvulsive dose of strychnine to block strychnine-sensitive glycine receptors (Gly1), glycine enhances, rather than inhibits, NMDA-induced convulsions. Together, these results indicate that the seizure-potentiating effects of glycine involve activation of NMDA receptors. This study provides the first evidence that glycine is capable of modulating the activity of NMDA receptors in the spinal cords of adult animals. In light of the elevated concentrations of glycine found in epileptogenic brain foci, these data also suggest that glycine may be a positive modulator in the production of epileptic seizures.
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PMID:Glycine potentiates strychnine-induced convulsions: role of NMDA receptors. 290 14

The effects of stereoisomers of gamma-glutamylaminomethylsulphonic acid (GAMS) on convulsions produced by intracerebroventricular injections of excitatory amino acids were studied in mice. gamma-D-GAMS preferentially blocked myoclonic seizures induced by kainate and had less pronounced anticonvulsant effect against quisqualate, N-methyl-D-aspartate, quinolinate, D-homocysteine sulphinate and L-glutamate. gamma-L-GAMS displayed only a relatively weak protective effect against kainate- and, to some extent, quisqualate-induced seizures, with little or no effect on the convulsant properties of the other excitatory amino acids. These results indicate that the D configuration of the gamma-carbon atom of excitatory amino acid antagonists is preferred not only for NMDA receptor antagonism but for antagonism at non-NMDA receptors as well.
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PMID:Anticonvulsant action of stereoisomers of gamma-glutamylaminomethylsulphonic acid in mice. 299 Sep 54

The evidence for an involvement of QUIN in human seizure disorders is clearly circumstantial. Importantly, QUIN is not a classical neurotransmitter and may thus play only a negligible or no role at all in normal brain function (Foster et al., 1984). We have yet to understand if and how such a possibly inert metabolite may turn into a pathogen. Several crucial questions remain to be addressed before a case can be made for a 'quinolinic acid hypothesis' of temporal lobe epilepsy. Among the most prominent ones figure the extracellular concentration of QUIN in the human brain under normal and pathological ('epileptic') conditions, the relationship between QUIN metabolism in the brain and its extracellular concentration and, a related issue, the regulation of cerebral QUIN metabolism (i.e., turnover). It is of equal importance to assess if NMDA-receptors, particularly those in the hippocampus and other parts of the limbic system, can exert a modulatory function upon brain QUIN. Unquestionably, future experiments with selective NMDA-antagonists will prove useful for the elucidation of such possible (feedback) interactions.
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PMID:Quinolinic acid: a pathogen in seizure disorders? 302 66

The participation of excitatory neurotransmitter systems in the basal ganglia in the initiation and propagation of limbic seizures induced by pilocarpine has been investigated in the rat. Limbic seizures (electrographic and motor) occur in rats receiving bilateral microinjections into the entopeduncular nucleus of 12.5 nmol N-methyl-D-aspartate or 0.1 nmol kainate, 15 min prior to a subconvulsant dose of pilocarpine (150 mg/kg, intraperitoneally). N-Methyl-D-aspartate (12.5 nmol) or kainate (0.5 nmol), injected alone bilaterally into the entopeduncular nucleus, induce sniffing and grooming but no electrographic or behavioural seizures. Limbic seizures also occur after a subconvulsant dose of pilocarpine when it is preceded by injection of N-methyl-D-aspartate (12.5 nmol) or kainate (0.5 or 2 nmol) into the dorsal striatum. Behavioural and electrographic signs of limbic seizures following pilocarpine (380 mg/kg) are suppressed by the focal microinjection into the entopeduncular nucleus of the N-methyl-D-aspartate antagonist, 2-amino-7-phosphonoheptanoate (0.02 nmol) or the kainate antagonist, gamma-D-glutamylamino-methylsulphonate (40 nmol). Seizure threshold within the limbic system is modulated by excitatory systems controlling basal ganglia outputs. The relative importance of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor systems varies between different components of the basal ganglia.
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PMID:Regulation of seizure threshold by excitatory amino acids in the striatum and entopeduncular nucleus of rats. 307 70

The novel glycine-prodrug anticonvulsant, milacemide (2-N-pentylaminoacetamide) (500 mg/kg), significantly increased (greater than 400% the seizure threshold induced by hyperbaric oxygen (4.5 atmosphere). This effect was significantly reduced by the selective inhibition of monoamine oxidase B by 1-deprenyl (2.0 mg/kg). 1-Deprenyl alone hardly affected the seizure threshold. These results suggest that, in the brain, milacemide is oxidized to glycine and that this reaction is mediated primarily by monoamine oxidase B. However, the interaction of milacemide metabolites (glycine amide, pentanoate and glycine) as antagonists of receptors of the glutamate NMDA (N-methyl-D-aspartate) subtype cannot be excluded.
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PMID:The glycine-prodrug, milacemide, increases the seizure threshold due to hyperbaric oxygen; prevention by 1-deprenyl. 313 41

The effects of daily focal injections of excitatory amino acid antagonists into the prepyriform cortex on the development of electrically kindled seizures at this site were studied. The selective 'NMDA receptor' antagonists 2-amino-7-phosphonoheptanoic acid (AP7) and 3-[+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) significantly inhibited the development of the electrically evoked afterdischarge over a 10 day period and prevented the development of the motor seizure responses. The 'kainate and quisqualate receptor' antagonist gamma-D-glutamylaminomethyl sulphonic acid (GAMS) showed less potent but still significant inhibitory actions on these responses. When drug treatment ceased, kindling progressed in all animals at a rate similar to that of the control (buffer-treated) animals. These results suggest a critical role for NMDA receptors in the primary neuronal events initiating the epileptiform activity in this animal model of epilepsy.
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PMID:Inhibition of the development of electrical kindling of the prepyriform cortex by daily focal injections of excitatory amino acid antagonists. 320 34

N-Methyl-D-aspartate (NMDA) (10 to 20 nmol) or bicuculline (15 to 50 pmol) in 0.5 microliter was infused bilaterally into the inferior colliculus or the deep layers of superior colliculus (DLSC) in normal rats, and the response to high intensity acoustic stimulation was examined. Thirty-five percent of rats receiving NMDA infusions and 42% of animals receiving bicuculline infusions into the inferior colliculus exhibited sound-induced seizures exclusively that were behaviorally similar to audiogenic seizures displayed by genetically epilepsy-prone rats. Rats receiving microinjections into the DLSC did not display sound-specific seizures. A combined pattern of spontaneous and sound-induced seizures was seen in some rats with both drugs and loci of microinjection. These data and previous studies support a role for increased excitant amino acid action and decreased efficacy of GABA in the inferior colliculus as important mechanisms involved in genetic susceptibility to audiogenic seizures.
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PMID:Induction of audiogenic seizure susceptibility by focal infusion of excitant amino acid or bicuculline into the inferior colliculus of normal rats. 351 85

We used limbic seizures induced in rats by systemic injection of the cholinergic agonist pilocarpine (380 mg/kg; i.p.) to study the neuronal pathways within the basal ganglia that modulate seizure threshold. N-Methyl-D-aspartate (N-Me-D-Asp) is an excitatory amino acid derivative that is a powerful convulsant agent when injected into the cerebral cortex, amygdala, or hippocampus in rats. Bilateral microinjections of N-Me-D-Asp into the caudate-putamen, however, protected against limbic seizures induced by pilocarpine (injected systemically), with an ED50 of 0.7 nmol (range 0.5-1.0 nmol). Lesioning the caudate-putamen (by bilateral microinjection of the excitotoxin ibotenate) converted subconvulsant doses of pilocarpine into convulsant ones. The anticonvulsant action of N-Me-D-Asp in the caudate-putamen was reversed by blocking gamma-aminobutyrate-mediated inhibition in the substantia nigra pars reticulata or in the entopeduncular nucleus. The results suggest that the caudate-putamen and its gamma-aminobutyrate-dependent efferent pathways modulate the threshold for seizures in the limbic forebrain.
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PMID:Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-D-aspartate in the rat caudate-putamen. 355 Jul 95

The neurotoxic and convulsant properties of conformationally restricted and synthetic analogues of excitatory acidic amino acids were examined after stereotaxic injection into the striatum and the dentate gyrus of the hippocampal formation. In the striatum, neurotoxicity was quantified by the reduction in the activity of choline acetyltransferase and glutamate decarboxylase, markers for striatal intrinsic neurons. The following sequence of neurotoxic potencies was defined; kainic acid approximately equal to domoic acid much greater than alpha-keto kainic acid approximately equal to alpha-allo kainic acid greater than ibotenic acid approximately equal to cis-cyclopentyl glutamic acid greater than quisqualic acid approximately equal to N-methyl-D-aspartic acid. When normalized for neurotoxic potencies, a wide variation in the convulsant effects of the agents was observed after hippocampal injection. N-Methyl-D-aspartate produced nearly continuous electroencephalographic seizures for 2 hr after injection, where alpha-keto-kainate and kainate and quisqualate caused seizure activity for 64 and 45% respectively of this period; kainate, alpha-allo kainate and domoate caused intermittent seizure activity during approximately 30% of the recording period; ibotenate and cyclopentylglutamate had minimal convulsant effects. Seizures were associated with a significant reduction in the levels of norepinephrine and with increases in the levels of 5-hydroxyindoleacetic acid in the cortex and hippocampal formation and increases in the levels of gamma-aminobutyric acid in the hippocampal formation. Kainate, domoate, keto-kainate and alpha-allo-kainate caused extensive lesions of the hippocampal formation that also involved the pyriform cortex; ibotenate and cyclopentylglutamate caused uniform but substantial lesions limited to the dentate gyrus, whereas quisqualate and N-methyl-D-aspartate produced small and restricted lesions. The results demonstrate a poor correlation between the neurotoxic and convulsant potencies of these excitatory amino acid analogues and suggest that receptor-specific interactions may account for these disparities.
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PMID:Excitatory amino acid analogues: neurotoxicity and seizures. 706 5


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