Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the effects of four weeks of dietary lithium treatment and of status epilepticus induced by administration of pilocarpine to lithium-treated rats on the concentrations of amino acids in four regions of rat brain: cerebral cortex, hippocampus, striatum, and substantia nigra. To ensure accurate quantitation of the amino acids, animals were sacrificed by focussed beam microwave irradiation and amino acids were measured using a fully validated triple-column ion-exchanged amino acid analyzer with post-column o-phthalaldehyde derivatization and fluorometric detection. The concentrations of four amino acids, threonine, methionine, lysine and tyrosine, were increased significantly in two to four brain regions by chronic lithium treatment. Their concentrations remained elevated, or were further increased, during status epilepticus. The concentrations of eight amino acids and ammonia were not altered by lithium treatment but increased in concentration during status epilepticus in some brain regions. Glycine, serine, arginine and citrulline were decreased by chronic lithium treatment. Status epilepticus increased the concentrations of these four amino acids above that found in the lithium-treated samples in some of the brain regions that were examined. Six amino acids and glutathione were generally unaltered by both treatments. These results are related to the effects of lithium treatment and are compared with changes reported by others following treatment with a variety of convulsive stimuli.
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PMID:Chronic lithium treatment and status epilepticus induced by lithium and pilocarpine cause selective changes of amino acid concentrations in rat brain regions. 259 48

It has been suggested that nitric oxide (NO) interferes with both glutamatergic neurotransmission and the regulation of cerebral blood flow in epileptic seizures. This study examines the effect of an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg), on the extracellular concentration of glutamate during seizures induced by kainic acid (KA; 10 mg/kg), both drugs being administered systemically. L-NAME was injected 40 min before KA. The extracellular glutamate concentration was measured in the hippocampus of awake, spontaneously breathing rats using microdialysis combined with HPLC. The arterial blood gases and glycemia were periodically checked. The arterial blood pressure, the electrocorticogram and the body temperature were continuously monitored. In basal conditions, the systemic injection of L-NAME increased arterial blood pressure but did not significantly change the hippocampal glutamate level. In seizure conditions, the hippocampal glutamate concentration was either slightly increased or not significantly changed in saline-treated rats (n = 6) but it was decreased in L-NAME-treated rats (n = 6). At all times after KA injection, the hippocampal glutamate concentration was significantly lower in L-NAME-treated rats than in saline-treated rats. Unlike saline-treated rats, L-NAME-treated rats died during status epilepticus. This study shows that acute systemic injection of L-NAME reduces the extracellular concentration of glutamate in the rat hippocampus during seizures induced by KA.
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PMID:Effect of inhibiting NO synthesis on hippocampal extracellular glutamate concentration in seizures induced by kainic acid. 760 44

We investigated whether the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) affects the cerebrovascular changes occurring in seizures induced by kainic acid (KA) in awake, spontaneously breathing rats. Blood flow and tissue PO2 and PCO2 were continuously and simultaneously measured by mass spectrometry from a cannula chronically implanted into the dorsal hippocampus, L-NAME (20 mg/kg; n = 8) or saline (n = 9) was administered i.p. 30 min prior to i.p. KA (10 mg/kg) injection. L-NAME significantly decreased hippocampal blood flow and PO2 and increased mean arterial blood pressure (MABP). In L-NAME-treated rats, seizure activity occurred about 10 min sooner than in control rats, and status epilepticus was inevitably followed by a flat electroencephalogram and sudden death. In contrast, control rats survival KA-induced seizures. Hippocampal blood flow was significantly less elevated during the seizures in L-NAME-treated rats than in control rats (maximal levels, 170 and 450%, respectively, of baseline values), though MABP remained significantly higher. Hippocampal PO2 was significantly decreased at all times after KA injection in L-NAME-treated rats, whereas it remained at or above normoxic levels in control rats. The present results show that L-NAME markedly attenuates the hippocampal blood flow and tissue PO2 changes in response to enhanced metabolic activity due to limbic seizures and suggest that NO is of major importance in cerebral blood flow control during KA-induced seizures.
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PMID:Blockade of nitric oxide synthesis inhibits hippocampal hyperemia in kainic acid-induced seizures. 801 4

The mechanisms by which neurons die after stroke and status epilepticus and related neuropathological conditions are unclear, but may involve voltage-dependent Na+ channels, glutamate receptors, and nitric oxide (NO.). These questions were investigated using an in vitro primary cell culture model in which hippocampal pyramidal neurons undergo a gradual and delayed neurodegeneration induced by enhanced excitatory neurotransmission. When cells were treated with Mg2+-free, glycine-supplemented medium for a brief period (15 min) and examined 24 h later, approximately 30-40% of the neurons had died. Cell death could be inhibited by blockers of voltage-sensitive Na+ channels and by N-methyl-D-aspartate receptor antagonists. Application of either the endogenous antioxidant melatonin (EC50: 19.2+/-2.8 microM) or the NO. synthase inhibitor Nomega-nitro-L-arginine after, but not during, Mg2+-free exposure protected against delayed neuronal death; significant neuroprotection was observed when the addition was delayed for up to 4 h. This operational time window suggests that an enduring production of NO. and reactive oxygen species from neuronal sources is responsible for delayed cell death. A role for reactive oxygen species in this injury process was strengthened by the finding that, whereas neurons cocultured with astroglia were more resistant to killing, agents capable of lowering intracellular glutathione negated this protection. Because secretion levels of melatonin are decreased with aging, reductions in this pineal hormone may place neurons at a heightened risk for damage by excitatory synaptic transmission.
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PMID:Melatonin prevents the delayed death of hippocampal neurons induced by enhanced excitatory neurotransmission and the nitridergic pathway. 961 51

The glutamate extracellular concentration is controlled by metabolic and neuronal pathways via release and uptake mechanisms. Stimulation of glutamate receptors induces neuronal nitric oxide (NO) release, which in turn modulates glutamate transmission. In this study, the influence of neuronally derived NO on hippocampal glutamate extracellular concentration was investigated in conditions of intense metabolic activation, i.e., during status epilepticus induced by systemic kainic acid (KA). Glutamate, arginine and citrulline concentrations were measured by microdialysis coupled to HPLC. Experiments were performed in conscious rats implanted with a microdialysis probe within the hippocampal CA3 area. Three groups were used: (1) rats treated with KA i.p. (12 mg/kg) and vehicle locally, via the microdialysis probe (n = 9); (2) rats given KA i.p. and a selective inhibitor of neuronal NO synthase, 7-nitroindazole (7-NI, 1.25 mM) locally (n = 13); (3) rats treated with saline i.p. and 7-NI locally (n = 7). Infusion of 7-NI or vehicle was performed throughout the second hour of status epilepticus. In groups 1 and 3, no significant modifications of extracellular glutamate, arginine and citrulline concentrations were measured. In group 2, the local application of 7-NI in the hippocampus during status epilepticus significantly increased extracellular glutamate and arginine concentrations, whereas citrulline concentration remained constant. The concomitant increases of extracellular glutamate and arginine concentrations under local 7-NI perfusion in seizure conditions, suggest that glutamate and arginine are linked in a common metabolic pathway and/or that glutamate is involved in the cross-talk between glia and neurons. A cerebrovascular effect of 7-NI which triggers glutamate release may also occur.
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PMID:7-Nitroindazole, a selective inhibitor of nNOS, increases hippocampal extracellular glutamate concentration in status epilepticus induced by kainic acid in rats. 1051 54

The effects of various doses of L-arginine, a nitric oxide substrate, on lithium-pilocarpine-induced seizures were studied in rats. Rats were implanted with chronic, stainless steel screw electrodes epidurally for electrocortical recordings. A control group received 3 mEq/kg LiCl (i.p.) and 24 h later 45 mg/kg pilocarpine HCl (i.p.). Two different experimental procedures were followed: (1) L-arginine was applied in doses of 100 mg/kg, 300 mg/kg or 500 mg/kg (i.p.), 30 min before pilocarpine injection; (2) 300 mg/kg, 500 mg/kg or 1000 mg/kg (i.p.) L-arginine was injected either 5 min or 30 min after the onset of status epilepticus (SE). L-arginine (300 mg/kg) injected 30 min before pilocarpine significantly reduced the percentage of SE, but did not change the latency to SE or 24-hour survival. These parameters were not significantly affected by the 100 mg/kg or 500 mg/kg dose of L-arginine. On the other hand, no dose of L-arginine that was applied after SE had begun, had any significant influence on the seizures. We concluded that L-arginine may prevent seizure activity in some but not all doses, and does not have any effect on the ongoing seizure activity.
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PMID:Effects of L-arginine on prevention and treatment of lithium-pilocarpine-induced status epilepticus. 1104 26

This report addresses the verification of the hypothesis that arginine-vasopressin affects the formation of hyperthermia-evoked convulsions in early ontogenesis in rats on days 3, 5, 7, and 9 of postnatal life. The modification of experimental febrile convulsions by PACAP (pituitary adenylate cyclase-activating peptide) was investigated; PACAP is a physiological regulator of the neurosecretion of arginine-vasopressin. Arginine-vasopressin (10 microg/rat) and PACAP (0.01 microg/rat) decreased the latency of generalized tonic-clonic convulsions and the time of truncal generalization of convulsive activity on days 3 and 5 of rat development. Animals given arginine-vasopressin (0.1-10 microg/rat) sowed significant increases in the duration of generalized convulsions to the level of status epilepticus on day 9 of life. Conversely, administration of higher doses of PACAP (0.1 microg/rat) increased the threshold of tonic-clonic convulsions on days 3 and 5 and decreased it on days 7 and 9 of postnatal development. The indirect involvement of PACAP in the mechanisms of experimental febrile convulsions is suggested to act via changes in arginine-vasopressin neurosecretion.
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PMID:Peptidergic mechanisms of hyperthermia-evoked convulsions in rats in early postnatal ontogenesis. 1240 2

Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to pharmacologic rescue, at 3-4 weeks of life. In the current report, we characterized amino acid profiles in SSADH(-/-) brain utilizing whole brain and regional extracts (frontal and parietal cortex, hippocampus, and cerebellum) to develop hypotheses concerning epileptogenesis. Of 35 amino acids quantified, we found significant dysregulation in SSADH(-/-) mice for 11 (GABA, glutamate, glutamine, alanine, aspartate, serine, taurine, cystathionine, methionine, homocarnosine, and arginine) as compared to age-matched littermates both before, and following, the period of generalized convulsive seizures and status epilepticus. Our results reveal imbalanced amino acid levels potentially involved in the transition from absence seizures to generalized convulsive seizures resulting in SSADH(-/-) mice. We conclude that the SSADH(-/-) mouse represents a unique epileptic model with the potential to reveal novel aspects of excitatory/inhibitory interactions in the genesis of seizures.
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PMID:Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency. 1526 67

We encountered an 11-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who developed occipital lobe epilepsy at the age of 7 years and 4 months. Thereafter she had repeated status epilepticus associated with stroke-like episodes. Status epilepticus consisted of repetitive complex partial seizures with or without secondarily generalized tonic clonic seizures. The seizures did not respond to conventional anticonvulsive drugs, including diazepam, midazolam, phenytoin, lidocaine, chloral hydrate, and thiamylal sodium, and lasted for several hours (mean 9.5 hours). At the age of 11 years, intravenous infusion of L-arginine (0.5 g/kg body weight) was first given five hours after the onset of status epilepticus. The seizures and electroencephalographic abnormalities improved dramatically. After the introduction of L-arginine, in addition to shortened duration of status epilepticus (mean 3 hours), clinical recovery from the status epilepticus was prompt, and the average hospitalization periods could be shortened. There were no obvious adverse effects, including vomiting, hypotension, and urticaria. Our experience suggests that early intravenous administration of L-arginine may be useful in the treatment of status epilepticus associated with stroke-like episode in patients with MELAS.
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PMID:[Usefulness of L-arginine infusion for status epilepticus in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes]. 1722 17

Status epilepticus results in preferential neuronal cell loss in the hippocampus. We evaluated the hypothesis that the repertoire of intracellular events in the vulnerable hippocampal CA3 subfield after induction of experimental temporal lobe status epilepticus entails upregulation of nitric oxide synthase II (NOS II), followed by the release of mitochondrial cytochrome c that triggers the cytosolic caspase-3 cascade, leading to apoptotic cell death. In Sprague-Dawley rats, significant and temporally correlated upregulation of NOS II (3-24h), but not NOS I or II expression, enhanced cytosolic translocation of cytochrome c (days 1 and 3), augmented activated caspase-3 in cytosol (days 1, 3 and 7) and DNA fragmentation (days 1, 3 and 7) was detected bilaterally in the hippocampal CA3 subfield after elicitation of sustained seizure activity by microinjection of kainic acid into the unilateral CA3 subfield. Application bilaterally into the hippocampal CA3 subfield of a selective NOS II inhibitor, S-methylisothiourea, significantly blunted these apoptotic events; a selective NOS I inhibitor, N(omega)-propyl-l-arginine or a potent NOS III inhibitor, N(5)-(1-iminoethyl)-l-ornithine was ineffective. We conclude that upregulation of NOS II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following the induction of experimental temporal lobe status epilepticus.
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PMID:Upregulation of nitric oxide synthase II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat. 1733 42


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