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

Audiogenic seizure (AGS)-susceptible DBA/2 (D2) mice have a significant reduction in brain Ca2+-ATPase activity compared to AGS-resistant C57BL/6 (B6) mice. This reduction is inherited together with AGS susceptibility in B6 X D2 recombinant inbred strains. The Ca2+-ATPase reduction occurs in microsomes and synaptosomes, but not in mitochondria. This enzyme activity is measured at a high Ca2+ concentration (2 mM) with no added Mg2+ or EGTA. We further studied this Ca2+-ATPase activity and a Mg2+-dependent (Ca2+ + Mg2+)-ATPase activity in synaptic plasma membranes (SPM) from the B6 and D2 strains. Using EGTA or CDTA to adjust free Ca2+ concentrations, we measured Ca2+-ATPase activities at Ca2+ concentrations from 0.8 microM to 436 microM. The Ca2+-ATPase activity is consistently lower in the D2 than in the B6 SPM over all Ca2+ concentrations. The basal Mg2+-ATPase activity measured at 2 mM MgCl2, is also lower in SPM of D2 than B6 mice. Calcium stimulates the basal Mg2+-ATPase activity to the same extent in the SPM of the B6 and the D2 mice. Maximum stimulation in both strains occurs at 150 microM added CaCl2 (buffered with 100 microM EGTA). Higher Ca2+ concentrations inhibit this ATPase activity similarly in both strains. The EGTA-EDTA washing of SPM significantly reduces by 50% of the (Ca2+ + Mg2+)-ATPase activities of both strains, whereas calmodulin treatment restored these activities. Neither of these treatments, however, has any noticeable effects on the Ca2+-ATPase activities of the strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium ATPase activities in synaptic plasma membranes of seizure-prone mice. 293 83

DBA/2 mice are genetically prone to audiogenic seizures and, when compared with seizure resistant C57BL/6 mice, were found to have an increased density of beta-adrenergic receptors in their midbrain at the age of peak seizure susceptibility. Propranolol, a beta-receptor blocking agent, attenuated all stages of the seizure syndrome. However, a comparison of the effects of its d- and l-isomers suggested that propranolol's anticonvulsant activity was due to its local anesthetic-like action. Pindolol, a more potent beta blocker that is at least 100 times less potent than propranolol with respect to local anesthetic-like activity, produced anticonvulsant effects in approximately the same systemic dose range as propranolol. This indicates that pindolol's anticonvulsant activity could be due to beta blockade and, taken together, these data suggest that beta-adrenergic receptors may play a role in the expression of audiogenic seizures in these animals.
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PMID:A possible role for beta-adrenergic receptors in the expression of audiogenic seizures. 298 41

Genetic differences in susceptibility to chemically induced seizures were examined in various populations of mice. Three inbred strains: C57BL, DBA, and C3H and a heterogenous stock (HS) of mice were tested for sensitivity to seizures induced by 3-mercaptopropionic acid (MP) and flurothyl. Dose response curves were constructed for each population of mice with each agent by quantitating latencies to specific stages of seizures. Significant strain and sex differences were observed in sensitivity to MP-induced seizures. Rank order from least sensitive to most sensitive was C57BL, HS, DBA, and C3H. Sensitivity to flurothyl-induced seizures was also strain dependent, but the rank order of sensitivity was different than for MP. The least sensitive strain was C57BL followed by HS, C3H, and DBA. Analysis of GABA receptors in seven brain regions obtained from C57BL and DBA using 3H-muscimol to measure high affinity GABA binding did not reveal significant differences in receptor number between these two strains. It thus appears that different genetic factors influence susceptibility to MP-induced seizures than to flurothyl-induced seizures. Furthermore, there is probably little correlation between the number of high affinity GABA receptors and sensitivity to seizures.
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PMID:Genetic influences on GABA-related seizures. 301 Mar 38

L-Cycloserine dose-dependently inhibited the activity of gamma-aminobutyric acid (GABA)-transaminase (GABA-T) and elevated the level of GABA in whole mouse brain with a peak effect 3-4 hr after a single intraperitoneal injection. At a dose (30 mg/kg) which elevated the level of GABA almost 4-fold, L-cycloserine moderately increased the content of alanine and slightly reduced that of aspartate, glutamate and glycine in the brain. L-Cycloserine (10-30 mg/kg, p.o. or i.p.) prevented tonic seizures induced by 3-mercaptopropionic acid (3-MPA) and audiogenic seizures in DBA/2 mice, without affecting those evoked by pentylenetetrazol, bicuculline and electroshock. Similarly small doses of L-cycloserine reduced the level of cGMP in the cerebellum of rats, prevented its elevation by 3-MPA and attenuated the hypothalamically-elicited rage reaction in cats. Larger doses of L-cycloserine (greater than 30-100 mg/kg) impaired the performance of mice in the rotarod, chimney and horizontal wire tests, and reduced spontaneous locomotor activity of rats. Upon repeated administration the inhibitory effect of L-cycloserine on the activity of GABA-T and on seizures elicited by 3-MPA in mice increased. In contrast, the depressant action of L-cycloserine on motor performance and locomotion declined in subchronically-treated mice and rats. The levels of amino acids in brain after repeated administration did not differ markedly from those in acutely-treated mice. It is suggested that small doses of L-cycloserine, probably by increasing GABAergic inhibition, reduce hyperexcitability in the brain in acute- and subchronically-treated animals. Larger doses of L-cycloserine, possibly by inducing multiple neurochemical changes, evoke central depressant effects which diminish during subchronic treatment.
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PMID:L-cycloserine: behavioural and biochemical effects after single and repeated administration to mice, rats and cats. 301 1

2-Amino-6-trifluoromethoxy benzothiazole (PK 26124) prevented convulsions induced in rodents by maximal electroshock, inhibitors of the synthesis of gamma-aminobutyric acid (GABA) and ouabain, but was inactive against seizures provoked by GABA antagonists, unlike diazepam, chlordiazepoxide, phenobarbital and valproic acid. 2-Amino-6-trifluoromethoxy benzothiazole prevented seizures induced by sound stimuli in DBA/2 mice (ED50 = 0.66; 2.1 and 4.1 mg/kg, i.p. according to the seizure component), postural seizures in El mice (ED50 = 7.5 mg, i.p.) and seizures induced by photic stimulation in the baboon, Papio papio, at 4 and 8 mg/kg (i.v.). This spectrum of anticonvulsant activity closely resembles that reported previously for dicarboxylic amino acid antagonists. Indeed, PK 26124 prevented seizures induced by L-glutamate (ED50 = 8.5 mg/kg, i.p.) or by kainate (ED50 = 9.25 mg/kg, i.p.) and tremors induced by harmaline (ED50 = 2.5 mg/kg, i.p.) In these tests diazepam was inactive (L-glutamate) or as potent as PK 26124 (kainate, harmaline), whereas it was 10-20 times more potent than PK 26124 against seizures induced by inhibitors of the synthesis of GABA. Together, these data suggest that PK 26124 possesses antagonistic properties of excitatory dicarboxylic amino acids, which may contribute to its anticonvulsant action.
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PMID:2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission--I. Anticonvulsant properties. 301 17

Various populations of mice exhibit differential sensitivity to seizure-inducing agents. The relationship of seizure susceptibility to alterations in the GABA receptor complex was investigated in six different populations of mice consisting of four inbred strains (C57BL, DBA, C3H, and BALB) and two selected lines (long sleep and short sleep). Seizure activity was induced by intraperitoneal administration of the GAD inhibitor, 3-mercaptopropionic acid, and latencies to seizure onset and tonus were measured. In naive mice of the same populations, GABA enhancement of 3H-flunitrazepam binding was measured in extensively washed whole brain membranes at several GABA concentrations. Both differential seizure sensitivity to 3-mercaptopropionic acid and differential enhancement of 3H-flunitrazepam binding by GABA were observed in these six populations of mice. Correlational analyses indicated a positive correlation between the degree of GABA enhancement of 3H-flunitrazepam binding and resistance to the seizure-inducing properties of 3-mercaptopropionic acid. These data suggest that genetic differences in sensitivity to seizure-inducing agents that disrupt the GABAergic system may be related to differences in coupling between the various receptors associated with the GABA receptor complex.
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PMID:Correlation between the enhancement of flunitrazepam binding by GABA and seizure susceptibility in mice. 303 5

The clinical utility of the carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ) is limited because of rapid development of tolerance to its effects. Tolerance is thought to develop as a result of glial cell proliferation and/or increased CA synthesis. DBA mice, susceptible to audiogenic seizures (AGSs) in an age-dependent manner, have increased CA activity as compared with C57 (non-audiogenic seizure susceptible) mice at 21 and 110 days of age. The present work utilized ACTZ to help determine the relationship between increased CA activity in brain and AGSs in DBA mice. Also, minimal electroshock seizure threshold (EST) was measured at various ages in DBA and C57 mice to determine age-related changes in CNS excitability. EST was significantly lower in DBA as compared with C57 mice at 18 days and between 40 and 115 days of age, suggesting that DBA mice remain hyperexcitable to electrical stimulation after they develop resistance to AGSs. ACTZ ED50s against maximal electroshock seizures (MES) were significantly higher in DBA as compared with C57 mice at 26,36, and 115 days of age. This finding correlates with higher CA activity in this strain at 110 days of age, noted previously. However, at 21 days of age, when CA activity is also higher in DBA versus C57 mice, there were no significant differences in ACTZ ED50s against MES between the strains. ACTZ ED50s against AGSs in DBA mice were considerably lower than ACTZ ED50s against MES in either strain, suggesting that a particular fraction of CA is intimately involved in the production of AGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic acetazolamide administration in DBA and C57 mice: effects of age. 308 35

The anticonvulsant activity of 1-bis(4-fluorophenyl)methyl-4-(3-phenyl-2-propenyl)-piperazine, flunarizine, was studied after intraperitoneal administration in DBA/2 mice (seizures induced by sound), intravenous administration in Papio papio (myoclonus induced by photic stimulation) and oral administration in Wistar rats (seizures induced by cefazolin). Protection against sound-induced seizures was observed after intraperitoneal administration of flunarizine (5-40 mg/kg). The ED50 for suppression of tonic, clonic and wild running phases of sound-induced seizures was 3.3, 9.8 and 17.5 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (50 mg/kg, i.p.). In photosensitive baboons flunarizine (0.5-1.0 mg/kg, i.v.) provided partial protection against myoclonic responses to stroboscopic stimulation. After flunarizine (2 mg/kg, i.v.) this protection lasted for more than 5 hr (and was complete at 2-3 hr). Cefazolin-induced seizures in rats were prevented by administration of flunarizine (20-40 mg/kg, orally). The ED50 for the suppression of tonic and clonic seizures evoked by subsequent intravenous administration of cefazolin was 25 mg/kg. The protective effects of flunarizine (40 mg/kg, orally) were maximal after 3-6 hr and were maintained for 16-24 hr. Behavioural effects of flunarizine included signs of sedation in both mice and rats. Tolerance to the antiepileptic effects of flunarizine was not seen after chronic treatment in rats. The role of purinergic receptors and of calcium entry blockade in the anticonvulsant action of flunarizine requires further study.
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PMID:Anticonvulsant properties of flunarizine on reflex and generalized models of epilepsy. 309 26

The mechanism by which animals develop tolerance to the antiepileptic effects of the carbonic anhydrase (CA) inhibitor, acetazolamide, was explored using a quantitative immunocytochemical method. Cerebral cortex sections of DBA/2J mice susceptible to audiogenic seizures and of C57BL/6J nonsusceptible mice were stained with antibody to mouse CA II in controls and following treatment with acetazolamide (40 and 200 mg/kg) for 1, 3, and 5 days. The percentage increases in CA II fluorescent intensity of cells from C57 mice treated with 40 and 200 mg/kg acetazolamide over those of untreated mice were 22 and 36%, respectively, after 1 day, 32 and 40%, respectively, after 3 days, and 17 and 40%, respectively, after 5 days of treatment. The corresponding percentage increases in fluorescent intensity of cells from DBA mice over controls were 13 and 32%, respectively, after 1 day, 17 and 41%, respectively, after 3 days, and 26 and 58%, respectively, after 5 days of treatment. The fluorescent intensity of cells from untreated DBA mice was 35% greater than those of untreated C57 mice. In C57 mice the maximum amount of CA II per cell at each dose occurred 24 h after acetazolamide treatment, whereas the amount in DBA mice continued to increase with time and dose up to 5 days. The differences between the two strains can be explained by changes in distribution of CA II to subcellular locations or by defects in phosphorylation of the molecule.
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PMID:Induction of new carbonic anhydrase II following treatment with acetazolamide in DBA and C57 mice. 309 10

The anticonvulsant activity of N-[beta-[4-beta-phenylethyl)phenyl]-beta-hydroxyethyl]-imidazole hydrochloride, denzimol, was studied following intraperitoneal administration in DBA/2 mice (seizures induced by sound). Protection against sound-induced seizures was observed after intraperitoneal administration of denzimol (3-15 mg/kg). The ED50 values for the suppression of tonic, clonic and wild running phases of sound-induced seizures were 1.24, 2.61 and 6.03 mg/kg, respectively. This protective action was significantly reduced by pretreatment with aminophylline (25 mg/kg i.p.), CGS 8216 (1 or 5 mg/kg i.p.) and Ro 15-1788 (2.5 mg/kg i.p). The present experiments suggest an involvement of purinergic and benzodiazepine mechanisms in the anticonvulsant action of denzimol.
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PMID:Anticonvulsant effect of denzimol in DBA/2 mice. 311 35


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