Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

In rat striatum, after one hyperbaric oxygen (HBO)-induced convulsion, polyamine changes are found that could promote N-methyl-D-aspartate (NMDA) activation. In the HBO-sensitive CD1 mouse, unlike in the common C57 strain, there is some support for NMDA activation after the HBO seizure. We measured PA cortical content before and after the first HBO-induced convulsion (about 608 kPa O2) in CD1 and C57 strains. Putrescine, spermidine and spermine were dansyl derived and analysed by HPLC. Exposure to HBO significantly increased putrescine content only in CD1 though a similar trend was observed in C57. No further increase was observed after convulsion whatever the strain. There were no significant changes in spermidine or spermine to support NMDA activation. Therefore, putrescine increase in CD1 cortex could reflect the free radical formation that is known to be greater in CD1 than in C57 mouse. Attempts to increase putrescine levels before HBO exposure hastened HBO-induced convulsion, less than spermidine or spermine. Because of physiological polyamine interconversion, additional experiments with indirect manipulation of putrescine levels and study of their time-course would precise these preliminary reports on putrescine and HBO.
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PMID:Effect of one hyperbaric oxygen-induced convulsion on cortical polyamine content in two strains of mice. 824 19

To distinguish the role of Mn superoxide dismutase (MnSOD) from that of cytoplasmic CuZn superoxide dismutase (CuZnSOD), the mouse MnSOD gene (Sod2) was inactivated by homologous recombination. Sod2 -/- mice on a CD1 (outbred) genetic background die within the first 10 days of life (mean, 5.4 days) with a complex phenotype that includes dilated cardiomyopathy, accumulation of lipid in liver and skeletal muscle, metabolic acidosis and ketosis, and a severe reduction in succinate dehydrogenase (complex II) and aconitase (a TCA cycle enzyme) activities in the heart and, to a lesser extent, in other organs. These findings indicate that MnSOD is required to maintain the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide. On the other hand, Lebovitz et al. reported an independently derived MnSod null mouse (Sod2tmlLeb) on a mixed C57BL/6 and 129Sv background with a different phenotype. Because a difference in genetic background is the most likely explanation for the phenotypic differences, the two mutant lines were crossed into different genetic backgrounds for further analyses. To study the phenotype of Sod2tmlLeb mice CD1 background, the Sod2tmlLeb mice were crossed to CD1 for two generations before the -/+ mice were intercrossed to generate -/- mice. The life span distribution of CD1 < Sod2-/- > Leb was shifted to the left, indicating a shortened life span on the CD1 background. Furthermore, the CD1 < Sod2-/- > Leb mice develop metabolic acidosis at an early stage as was observed with CD1 < Sod2-/- > Cje. When Sod2tmlCje was placed on C57BL/6J (B6) background, the -/- mice were found to die either during midgestation or within the first 4 days after birth. However, when the B6 < Sod2 -/+ > Cje were crossed with DBA/2J (D2) for the generation of B6D2F2 < Sod2-/- > Cje mice, an entirely different phenotype, similar to that described by Lebovitz et al., was observed. The F2 Sod -/- mice were able to survive up to 18 days, and the animals that lived for more than 15 days displayed neurological abnormalities including ataxia and seizures. Their hearts were not as severely affected as were those of the CD1 mice, and neurological degeneration rather than heart defect appears to be the cause of death.
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PMID:The use of transgenic and mutant mice to study oxygen free radical metabolism. 1067 32

The involvement of GABA(B) receptors in the behavioural and epileptic electrocortical discharges occurring in chemical kindling induced by repeated treatments with a subconvulsant dose of pentylenetetrazole (25 mg/kg i.p.) has been investigated in CD1 mice. Behavioural and electrocorticographic epileptic seizures following kindling induced by pentylenetetrazole (25 mg/kg i.p.) were attenuated or completely antagonized in a dose-dependent manner by the GABA(B) receptor agonist R-baclofen (2 and 6 mg/kg) whilst the GABA(B) receptor antagonist 3-amino-propyl-diethoxy-methyl-phosphinic acid (CGP 35348, 25, 50 or 100 mg/kg) and 3-[1-(S)-(3, 4-dichloro-phenyl-ethyl]amino-2-(S)-hydroxy-propyl-benzyl-phosphinic acid (CGP 55845A, 10 or 20 mg/kg) produced a more rapid development of kindling and an increase in behavioural and electrocorticographic epileptic changes. In addition, all GABA(B) receptor antagonists were able to induce an increase in Fos and Jun protein expression in pentylenetetrazole (25 mg/kg i.p.) treated mice whilst the GABA(B) receptor agonist R-baclofen (2 or 6 mg/kg) attenuated the expression of Fos and Jun protein, at cortical and limbic structures. In order to study the persistence of changes induced by pentylenetetrazole kindling, different groups of mice were rechallenged with a kindling stimulus 15 or 30 days after withdrawal from the last injection of vehicle+pentylenetetrazole, R-baclofen+pentylenetetrazole or GABA(B) receptor antagonists+pentylenetetrazole. The groups receiving GABA(B) receptor antagonists+pentylenetetrazole showed a higher incidence of seizures following the kindling stimulus than mice receiving vehicle+pentylenetetrazole whilst animals treated with R-baclofen were protected from the kindling stimulus. The different effects observed following repeated treatment with the GABA(B) receptor agonist and antagonist used revealed that GABA(B) receptors are able to affect the development of the epileptic kindling state induced by pentylenetetrazole.
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PMID:Effects of compounds acting on GABA(B) receptors in the pentylenetetrazole kindling model of epilepsy in mice. 1096 58

We compared the effects of adding a non-protective dose of valproate to increasing doses of lamotrigine with those of monotherapy and vice versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced by both 4-aminopyridine and pentylenetetrazole, and neurotoxic effects were evaluated by the rotarod test. Changes in anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate concentrations in the whole brain were also assessed. Lamotrigine increased the potency ratio of valproate against 4-aminopyridine and pentylenetetrazole but not on rotarod, the protective index being increased from 1.1 to 2.4 against 4-aminopyridine and from 1.9 to 3.8 against pentylenetetrazole, without changes in brain valproate, and with a significant increase in brain GABA. Valproate increased the potency ratio of lamotrigine against 4-aminopyridine but not on rotarod, the protective index being increased from 4.4 to 7.3; valproate also increased brain lamotrigine (but only at low doses), brain GABA and brain glutamate. In conclusion, non-protective doses of lamotrigine increased the therapeutic index of valproate and vice versa, and these effects appeared to be pharmacodynamic.
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PMID:Synergistic interaction between valproate and lamotrigine against seizures induced by 4-aminopyridine and pentylenetetrazole in mice. 1239 58

The May 2002 COM. A 38-year-old man presented with new onset seizures and a 69-year-old woman presented with bilateral headaches and episodes of syncope. Both were found to have extra-axial masses that were contrast-enhancing and thought to be meningiomas. Both had complete resection. Microscopic examination revealed an inflammatory lesion composed of plasma cells, scattered lymphocytes and numerous large histocytic cells, which exhibited emperi polesis and were CD1 a negative, but positive for CD68 and S100. The diagnosis of Destombes-Rosai-Dorfman Disease (DRDD) was rendered. Both cases had good long-term outcome. The differential diagnosis of inflammatory masses in the dura (plasmacytoma, lymphomas, plasma cell fibroma, angiofollicular hyperplasia [Castleman's-disease] and Langerhan's cell histiocytosis) are discussed.
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PMID:May 2002: 38-year-old man and 69-year-old woman with dural based masses. 1240 40

We compared the effects of adding a nonprotective dose of felbamate to increasing single doses of lamotrigine with those of monotherapy and vice versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced by both 14 mg/kg of 4-aminopyridine and 110 mg/kg of pentylenetetrazole, and neurotoxic effects were evaluated by the rotarod test. Changes in anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate concentrations in the whole brain were also assessed. Lamotrigine increased the potency ratio of felbamate against 4-aminopyridine (1.80, 95% confidence interval (CI) 1.23-2.65, P<0.05) but not against pentylenetetrazole nor on rotarod, the protective index being increased from 12.0 to 17.1 for 4-aminopyridine, with a reduction in brain felbamate, and with an increase in brain GABA. Felbamate increased the potency ratio of lamotrigine against 4-aminopyridine (4.35, 95% CI 2.05-9.25, P<0.05) but not on rotarod, the protective index being increased from 4.4 to 15.7; there were no changes in brain lamotrigine, and changes in brain GABA and/or glutamate were unrelated to the pharmacodynamic effects. In conclusion, a nonprotective dose of lamotrigine increased the therapeutic index of felbamate and vice versa, and these effects appeared to be pharmacodynamic.
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PMID:Synergistic interaction between felbamate and lamotrigine against seizures induced by 4-aminopyridine and pentylenetetrazole in mice. 1265 Aug 32

We compared the effects of adding a non-protective dose of valproate (VPA) to increasing single doses of felbamate (FBM) with those of monotherapy and vice versa in CD1 mice. Anticonvulsant effects were evaluated against seizures induced by 14 mg kg(-1) of 4-aminopyridine (4-AP) and by 110 mg kg(-1) of pentylenetetrazole (PTZ), and neurotoxicity by the rotarod test. The study also assessed changes in concentrations of anticonvulsants, gamma-aminobutyric acid (GABA) and glutamate in the whole brain. VPA increased the potency ratio of FBM against 4-AP (1.94, P<0.05) but not against PTZ. VPA increased the neurotoxicity of FBM (3.30, P<0.05) and the protective index of FBM was, therefore, reduced from 12.0 to 7.0 for the 4-AP model and from 11.8 to 5.2 for the PTZ model; VPA reduced brain FBM, and increased brain GABA in relation to FBM monotherapy. On the other hand, FBM increased the potency ratio of VPA against 4-AP (1.60, P<0.05) but not against the PTZ, and had no effect on the rotarod model. Therefore, the protective index increased from 1.1 to 1.6 for the 4-AP model and decreased from 1.9 to 1.7 for the PTZ model. FBM did not change brain VPA, and changes in brain GABA and glutamate were not clearly related to anticonvulsant effects. In conclusion, although the addition of a low dose of FBM to VPA was beneficial in the 4-AP model, the addition of a low dose of VPA to FBM was not; both combinations were disadvantageous in the PTZ model. This interaction appears to be pharmacodynamic because a pharmacokinetic mechanism was discarded.
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PMID:Is the interaction between felbamate and valproate against seizures induced by 4-aminopyridine and pentylenetetrazole in mice beneficial? 1279 71

Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.
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PMID:Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy. 1512 Jul 41

Ischemic brain injury from stroke is an important cause of disability in infants and children, but current experimental models for the disorder are complex. These preparations require occlusion of small intracerebral vessels or common carotid artery ligation combined with exposure to reduced levels of oxygen. Unilateral carotid artery ligation alone was sufficient to cause brain injury in more than 70% of 12-day-old CD1 mice. Using a blinded behavioral rating scale of seizure activity in mice, a direct, highly significant correlation between the severity of seizures over the 4-hour period after ligation and the severity of histologic brain injury 7 days later (Spearman's rho = 0.835, P < 0.001) was documented. This study presents the first model of stroke in immature mice produced by unilateral carotid artery ligation alone, and the first to demonstrate a clear correlation between acute ischemia-induced seizures and brain injury. This new model should be useful for examining the pathogenesis of stroke in the immature brain and the potential contribution of seizures to final outcome.
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PMID:A new model of stroke and ischemic seizures in the immature mouse. 1546 36

Increased hippocampal excitability constitutes a pathogenetic hallmark of pharmacoresistant human temporal lobe epilepsy (TLE). Metabotropic glutamate receptors (mGluRs) can be subdivided into three classes based on sequence homologies, mechanisms of signal transduction as well as pharmacological characteristics. Generally, class I mGluRs mediate neuronal excitation whereas activation of class II and III mGluRs decreases synaptic transmission. Changes in expression of class I and III mGluR subunits have been described in human TLE. It remains to be determined whether altered mGluR expression relates to differences in seizure susceptibility or hippocampal damage. Here, we examine the transcription levels of mGluRs class I (mGluR1 and 5) and III (mGluR4 and 7) in experimental TLE and correlate differential mGluR subunit expression with mouse-strain-dependent susceptibility to TLE induced by pilocarpine. Expression of mGluRs 1, 4, 5 and 7 was determined in epileptic dentate gyrus granule cells (DG) in CD1, C57BL/6 and FVB/N mice by real time RT-PCR. FVB/N mice appear significantly more vulnerable to pilocarpine-induced seizures than C57BL/6 and CD1 strains. RT-PCR analysis demonstrates an increased expression of inhibitory mGluR 4 and downregulation of excitatory mGluR 1 in epileptic CD1 mice and a decrease of the excitatory mGluRs 1 and 5 in C57BL/6 (p<0.05, n=6 each) but not in the FVB/N strain. These results correlate differential expression of excitatory class mGluR I and inhibitory class mGluR III to seizure susceptibility and hippocampal damage. Our data suggest mGluRs class I and III as interesting potential therapeutic targets to interfere with hippocampal epileptogenesis and hyperexcitability.
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PMID:Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy. 1569 59


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