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

Much evidence shows that glia regulates the cation and anion content of brain interstitial space. In rats the pH and bicarbonate (HCO3-) concentration of neurons and glia were derived from carbon 14-labeled HCO3- and dimethyloxazolidinedione uptake into brain and cerebrospinal fluid. Acetazolamide increases the total CO2 concentration in neurons and decreases the pH and HCO3- concentration in glia. Inhibition of glial carbonic anhydrase (CA) reduces conversion of neuronally derived CO2 to HCO3-, glial pH is lowered, and neuronal CO2 accumulates. CA therefore has an essential role in regulating pH in neurons, glia, and interstitial fluid. In audiogenic seizure mice, glial CA activity is increased and glial anion transport is reduced. As the mice age, seizure susceptibility, the increased CA activity, and the defect in anion transport disappear concurrently. The enhanced CA activity in the glial cells of these mice is an adaptive mechanism to overcome the defect in anion transport that results from a deficiency of HCO3- -dependent and Na+- and K+ -dependent adenosine triphosphatase. Pentylenetetrazol stimulates neurons in neonatal rats, but after 10 days of age, when glia is present, it too is stimulated and the seizures are attenuated. Cobalt implantation in the cortex of rats also induces a glial response that ameliorates the focal seizures produced by this procedure.
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PMID:Ionic and acid-base regulation of neurons and glia during seizures. 615 Jun 82

The properties of gamma-aminobutyric acid recognition sites, benzodiazepine binding sites and the effect of exogeneous gamma-aminobutyric acid on benzodiazepine binding were determined in crude membrane fractions prepared from the brains of DBA/2 mice at ages before (8-9 and 17-18 days), during (22-23 and 28-29 days) and after (40-43 days) the age of high susceptibility to audiogenic seizures. These have been compared with data from age-matched mice of a strain (TO) with lower audiogenic seizure susceptibility. The number of high-affinity [3H]gamma-aminobutyric acid binding sites was lower at all ages in DBA/2 mice compared with TO mice, but the affinity was higher in DBA/2 mice. The number of low-affinity [3H]gamma-aminobutyric acid binding sites was lower at 8-9 days and 40-43 days in DBA/2 mice, but was not significantly different from TO mice at other ages. For [3H]flunitrazepam binding, the only difference found was a slight reduction in the number of binding sites at 28-29 days of age in DBA/2 mice. gamma-Aminobutyric acid stimulation of [3H]flunitrazepam binding was not significantly different up to 22-23 days of age, but was higher in DBA/2 mice at 28-29 days and lower at 40-43 days. Impairment of gamma-aminobutyric acid function is a possible permissive factor in the age-dependent audiogenic seizure susceptibility in DBA/2 mice.
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PMID:gamma-Aminobutyric acid and benzodiazepine binding sites in audiogenic seizure-susceptible mice. 628 78

Intraperitoneal injection of ethanol (1-2 g/kg) and chlordiazepoxide (2-16 mg/kg) suppressed susceptibility to audiogenically induced, clonic-tonic seizures and antagonized forelimb tremor in rats undergoing ethanol withdrawal, 30 min after treatment. However, a smaller dose of ethanol (0.5 g/kg) actually increased clonic seizure frequency, suggesting that ethanol exerts a biphasic proconvulsant/anticonvulsant action. Direct activation of gamma-aminobutyric acid (GABA) receptors by intracisternal administration of GABA (100-1000 micrograms), muscimol (0.3-1.0 micrograms) or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) (0.3-3.0 micrograms) 5 to 10 min before testing also reduced susceptibility to audiogenic clonic-tonic seizures. In sharp contrast to these anticonvulsant actions, GABA, muscimol and THIP had no effect on withdrawal-induced forelimb tremors. Blockade of GABA uptake with 1-2,4-diaminobutyric acid (300 and 600 mg/kg i.p.) and inhibition of GABA transaminase with aminooxyacetic acid (12.5 and 25.0 mg/kg i.p.) both reduced susceptibility to seizures. However, anticonvulsant doses of these two drugs, unlike GABA, muscimol and THIP, also reduced forelimb tremor. Three other GABA transaminase inhibitors, gamma-vinyl GABA (450 and 900 mg/kg i.p.), gamma-acetylenic GABA (50-150 mg/kg i.p.) and ethanolamine-O-sulfate (250-750 mg/kg i.p.), were inactive against ethanol withdrawal audiogenic seizures and forelimb tremors. These results indicate that direct GABA receptor activation can selectively suppress one type of ethanol withdrawal response (i.e., audiogenic seizure susceptibility) while failing to influence another (forelimb tremors).
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PMID:Differential sensitivity of ethanol withdrawal signs in the rat to gamma-aminobutyric acid (GABA)mimetics: blockade of audiogenic seizures but not forelimb tremors. 631 80

The relative anticonvulsant potential of the gamma-aminobutyric acid (GABA) agonist, muscimol, was compared after microinjection into either the inferior colliculus, substantia nigra or medial septum of ethanol-dependent rats. Bilateral microinjection of muscimol (10-30 ng) into the inferior colliculus 15 to 60 min before testing suppressed all sound-induced seizure components (wild running, clonus and tonus) in rats withdrawn from ethanol for 6.5 to 8.5 hr. However, forelimb tremors were not altered. Audiogenic seizures were suppressed for at least 3 hr after muscimol (30 ng). In the medial septum and substantia nigra, microinjection of muscimol (30-100 ng) only partially reduced the tonic component of audiogenic seizures and exerted no effect on the frequency of wild running or clonus. GABA (10 micrograms) and two other GABA agonists [4,5,6,7-tetrahydroisoxazolo[5, 40c]pyridin-3-ol (THIP), 300 ng and chlordiazepoxide, 10-30 micrograms], microinjected into the inferior colliculus, also reduced audiogenic seizure susceptibility. However, 1, 3-butanediol, which suppresses ethanol withdrawal seizures after peripheral administration in rats, was inactive. The relative proconvulsant potential of the GABA antagonist, bicuculline methiodide, also was compared after microinjection into either the inferior colliculus, substantia nigra or medial septum of ethanol naive rats. In each animal, audiogenic seizure-like wild running, clonus and tonus were evoked by microinjecting bicuculline methiodide into the inferior colliculus at the rate of 6.0 ng/6 min. However, these reactions did not occur when bicuculline methiodide was applied at a slower rate (1.8 ng/6 min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of susceptibility to audiogenic seizures in ethanol-dependent rats after microinjection of gamma-aminobutyric acid (GABA) agonists into the inferior colliculus, substantia nigra or medial septum. 631 42

The anticonvulsant action of various aporphine derivatives that act on dopamine receptors has been investigated in two genetically determined animal models--DBA/2 mice with sound-induced seizures and baboons Papio papio with photically-induced seizures. Protection against the clonic and tonic phases of the seizures response in DBA/2 mice was seen for 15-60 min after (-)2,10,11-trihydroxy-N-n-propylnoraporphine (1.25 mg/kg) and (-)10,11-methyl-enedioxy-N-n-propylnoraporphine (0.625-1.25 mg/kg) and for 30-60 min after (-)2,10,11-trihydroxyaporphine (31.25 mg/kg). Short-lasting protection (up to 30 min) was seen following (-)2,10,11-trihydroxy-N-ethyl-noraporphine (1.25-6.25 mg/kg). Changes in audiogenic seizure susceptibility were accompanied by piloerection, ptosis and loss of spontaneous locomotor and exploratory behaviour. No protection was seen after (-)norapomorphine (0.05-18.75 mg/kg). All the compounds (including norapomorphine) significantly lowered rectal temperature, although the time course of this effect was often longer than that of protection against audiogenic seizures. In baboons, marked reductions in photomyoclonic responses were seen following (-)10,11-methylenedioxy-N-n-propylnoraporphine (0.25 mg/kg, lasting up to 2h); (-)2,10,11-trihydroxy-N-n-propylnoraporphine (0.5-2.5 mg/kg, lasting up to 7 h); (-)2,10,11-trihydroxyaporphine (5 mg/kg, duration of action 1-4 h) and (-)2,10,11-trihydroxy-N-ethylnoraporphine (6.25 mg/kg, lasting 2 h). Little change in responsiveness followed administration of (-)norapomorphine 1.25 or 6.25 mg/kg. Changes in photosensitivity were accompanied by yawning and pupil dilatation. (-)10,11-Methylenedioxy-N-n-propylnoraporphine (0.5-6.25 mg/kg) was also administered orally in baboons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative assessment of dopamine agonist aporphines as anticonvulsants in two models of reflex epilepsy. 641 43

The properties and distribution of beta-galactosidase were studied in the mouse brain using the artificial substrate methylumbelliferyl-beta-galactoside. Enzyme activities were compared between an audiogenic seizure-susceptible mouse strain (DBA/2) and three non-susceptible strains of mice (BALB/c, C3H/He and Swiss A2G). At all ages, DBA/2 mice have significantly lower beta-galactosidase activity compared with the three other mouse strains: this is attributed to the different alleles present at the Bgs locus. The low activity of beta-galactosidase is also evident when the natural substrate GMl-ganglioside is hydrolyzed. In contrast to this low GMl-ganglioside-beta-galactosidase activity, there is no difference in the activity of the second form of acid beta-galactosidase, galactosylceramidase, in DBA/2 mice at 7 and 14 days. However, at 21 and 28 days the activity is significantly lower in DBA/2 mice compared with the other strains of mice. These results on beta-galactosidase activity in the brain of seizure-susceptible and non-susceptible mice are discussed in relation to published levels of GMl-ganglioside and galactosylceramide present in the developing mouse brain.
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PMID:Substrate specificity and distribution of acid beta-galactosidase activities in seizure-susceptible and non-susceptible strains of mice. 643 23

Genetic animal models of epilepsy comprise genetically predisposed animal species in which seizures either occur spontaneously or in response to sensory stimulation. The major advantage of these naturally occurring epilepsies in animals as models of human epilepsy is that they simulate the clinical situation more closely than any other experimental epilepsy. Models with idiopathic spontaneous recurrent seizures are epileptic dogs, tottering mice, and rats with spike-wave absence (petit mal) seizures. In dogs, the most common seizure type are generalized tonic-clonic (grand mal) seizures. Recent epidemiological and antiepileptic drug efficacy studies strongly suggest that epileptic dogs offer a valuable model for human grand mal epilepsy. In tottering mice, two types of spontaneous recurrent seizures occur: spike-wave absence seizures and focal motor seizures. Both types differ in sensitivity to common antiepileptic drugs, which closely resembles the absence and focal types of epilepsy in humans. Spontaneously recurrent spike-wave absence seizures in rats can be selectively blocked by drugs effective in petit mal (absence) epilepsy in man, demonstrating the validity of this new petit mal model for anticonvulsant drug screening. Models with reflex seizures comprise photosensitive baboons (Papio papio) and fowl, audiogenic seizure susceptible mice and rats, and gerbils with seizures in response to different sensory stimuli. With respect to seizure types and drug efficacies in these species, rats and chickens may represent suitable models for grand mal epilepsy, whereas baboons offer a useful model of photomyoclonic seizures. Gerbils can be subdivided into animals with minor (myoclonic) and major (mostly generalized tonic-clonic) seizures, which respond differently to antiepileptic drugs and seem to provide interesting models for petit mal and grand mal epilepsy in man. In conclusion, the data summarized in this review emphasize that genetic animal models of epilepsy offer unique approaches to the evaluation of antiepileptic drugs used or usable in man.
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PMID:Genetic animal models of epilepsy as a unique resource for the evaluation of anticonvulsant drugs. A review. 643 66

The anticonvulsant effect of either phenobarbital or dilantin was potentiated by exogenous glycine in DBA/2 audiogenic seizure mice and in 3-mercaptopropionic acid-induced seizures. In seizures caused by pentylenetetrazol, glycine potentiated the anticonvulsant effect of phenobarbital only slightly; in combination with dilantin, which was ineffective by itself, it did not have an effect. Valproic acid, in large doses, prevented 3-mercaptopropionic acid-induced seizures; glycine did not potentiate its effect. Glycine thus potentiates anticonvulsant effects, but only of some drugs and only in some of the seizure models. This suggests that the mechanism of the anticonvulsant effect of glycine is similar to that of some of the anticonvulsant drugs such as dilantin and different from others, and that this mechanism is not effective in all seizure models.
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PMID:Glycine potentiates the action of some anticonvulsant drugs in some seizure models. 644 97

The subcellular distribution of amino acids was compared in brains of genetically seizure-susceptible (SS) and genetically seizure-resistant (SR) rats. The total taurine content (mumol/brain) in the P2B, or synaptosomal, fraction in SS rats was only 37% of that of SR rats. Glutamate, glutamine, glycine, alanine, and gamma-aminobutyric acid (GABA) contents were unaltered. No alterations in total content were found in other subcellular fractions for the amino acids studied. SS animals that had never been stimulated to audiogenic seizure had decreased concentrations of taurine (nmol/mg protein) in the P2, P2B, and P2C fractions as compared with SR animals. These fractions contain crude synaptosomes, enriched synaptosomes, and enriched mitochondria, respectively. Phosphoethanolamine concentrations were also decreased in the P2B fractions, but concentrations of other amino acids were unaltered, as compared with SR animals. Twenty-four hours after the intracerebroventricular injection of taurine (6 mumol) in SS animals that had never been convulsed, taurine concentrations were significantly increased in whole brain homogenate and P2 and P2B fractions as compared with SS animals not given taurine. This treatment left unaltered the concentrations of glutamate, glutamine, GABA, and glycine in brain homogenate and P2 fraction. Because decreases in taurine concentration were seen in animals that had not been convulsed, these alterations are intrinsic to the SS strain and are not a consequence of convulsive activity. In view of the antiepileptic action of taurine, and the fact that an impairment of taurine transport in the brain of SS rats had previously been demonstrated, we suggest that a defect in the biochemistry of taurine is partially responsible for the seizure susceptibility of the SS rat.
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PMID:Subcellular distribution of neuroactive amino acids in brains of genetically epileptic rats. 647 8

The proconvulsant and convulsant actions of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and of methyl-beta-carboline-3-carboxylate (beta-CCM) have been evaluated in two animal models of reflex epilepsy, the photosensitive baboon, Papio papio, and the audiogenic seizure prone DBA/2 mouse. In baboons, myoclonic responses to photic stimulation are markedly enhanced 1 min after DMCM, 0.25 mg/kg i.v. In the absence of photic stimulation DMCM, 0.5 mg/kg i.v. induces a single brief tonic clonic seizure within 10-90 s. beta-CCM, 0.025-0.05 mg/kg i.v. similarly enhances myoclonic responses to photic stimulation. Generalised seizures occur without photic stimulation 0.5-3 min after beta-CCM, 0.1-0.2 mg/kg. Pretreatment with the excitatory amino acid antagonist, 2-amino-7-phosphonoheptanoic acid (2-APH), 110 mg/kg i.v., prevents the generalised seizures induced by DMCM, 0.5 mg/kg, but not those induced by beta-CCM, 0.1-0.2 mg/kg. In DBA/2 mice beta-CCM and DMCM are indistinguishable in potency as convulsants (ED50 values for clonic seizures: 4.4 and 4.6 mg/kg i.p. respectively) and as proconvulsants (ED50 values for facilitation of clonic seizure responses to an 83 dB sound stimulus: 0.25 and 0.23 mg/kg). Pretreatment with 2-APH gives equipotent protection against audiogenic seizures induced by beta-CCM, 1 mg/kg or DMCM, 1 mg/kg. The differences in relative potency of beta-CCM and DMCM in the two species are probably accountable for in terms of differing metabolism. A differential action of the two beta-carbolines on receptor subtypes, with enhancement of excitatory amino acid release playing a more important role in epileptogenesis after DMCM, is proposed.
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PMID:Behavioural and convulsant actions of two methyl esters of beta-carboline-3-carboxylic acid in photosensitive baboons and in DBA/2 mice. 649 18


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