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)

The objective of the present study was to assess metabolic changes in the neocortex and hippocampus of well-oxygenated or moderately hypoxic rats in which fluorothyl-induced seizures were sustained for 5 or 20 min, or which were allowed recovery periods of 5, 15, or 45 min following cessation of 20-min seizure activity by withdrawal of the convulsant gas. Sustained fluorothyl-induced seizures were found to cause metabolic alterations qualitatively and quantitatively similar to those previously observed with other commonly used convulsants. Thus, although the phosphorylation state of the adenine nucleotide pool remained only moderately perturbed, if at all, there were decreases in tissue concentrations of phosphocreatine and glycogen, and increases in those of cyclic AMP, lactate, and pyruvate, with a calculated fall in intracellular pH of about 0.15 units and a rise in the cytoplasmic NADH/NAD+ ratio. The enhanced metabolic rate was reflected in a marked reduction in the tissue-to-plasma glucose concentration ratio. Induced moderate hypoxia (arterial PO2 40-50 mm Hg) had no metabolic effect after 5 min of seizures but moderately increased lactate concentrations after 20 min (from about 10 to about 15 mumol X g-1). On cessation of seizure discharge cyclic AMP and phosphocreatine concentrations normalized already within 5 min, whereas glycogen and lactate concentrations normalized more slowly. In the neocortex (but not the hippocampus) postepileptic tissue-to-plasma glucose concentration ratios rose above control, probably reflecting metabolic depression. The results suggest that intracellular pH promptly returned to control, and that postepileptic alkalosis developed. They also suggest that some elevation of the NADH/NAD+ ratio persisted even after 45 min of recovery.
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PMID:Cerebral metabolic changes during and following fluorothyl-induced seizures in ventilated rats. 398 40

The effects of pentylenetetrazol on behavior, EEG activity and regional CNS levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) in mice and guinea pigs were studied. Pentylenetetrazol increased cGMP levels in all regions of brain examined (cerebral cortex, hippocampus, striatum and cerebellum) and increased cAMP levels in all regions except striatum. cGMP levels were increased by both sub-convulsant and convulsant doses of pentylenetetrazol. In contrast, cAMP levels were elevated only by concentrations of pentylenetetrazol that produced clinically evident seizures or epileptiform EEG activity. These data indicate that increases in CNS cGMP levels produced by epileptogenic stimuli can occur independently of seizure discharges, whereas accumulation of cAMP requires and is secondary to seizure activity. In conjunction with results of other studies, these data support the hypothesis that cGMP may have a role in seizure genesis and/or propagation, whereas cAMP may be involved in processes that attenuate or terminate seizures.
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PMID:Relationships between seizure activity and cyclic nucleotide levels in brain. 625 46

Cerebrospinal fluid levels of gamma-aminobutyric acid (GABA) and cyclic nucleotides were measured in alcoholic and control patients. Alcoholics without seizures had higher GABA levels than either alcoholics with seizures or controls. Levels of cyclic AMP and cyclic GMP in cerebrospinal fluid of controls and alcoholics with and without seizures were not significantly different.
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PMID:Cerebrospinal fluid GABA and cyclic nucleotides in alcoholics with and without seizures. 626 55

Norepinephrine (NE) depletion of the cerebral cortex after lesion of the ipsilateral locus ceruleus (LC) causes abnormalities of cerebral oxidative metabolism when the cortex is stimulated to increased energy demand (Harik, S. I., J. C. LaManna, A. I. Light, and M. Rosenthal (1979) Science 206: 69-71; LaManna, J. C., S. I. Harik, A. I. Light, and M. Rosenthal (1981) Brain Res. 204: 87-101). These abnormalities were exhibited as decreased mitochondrial reducing equivalent flow. One possible cause of this would be the decreased availability of oxidative metabolic substrates in the NE-depleted cortex. We therefore investigated the effect of unilateral LC lesion and the resultant depletion of ipsilateral endogenous NE on glycogen and other energy metabolites in the cerebral cortex of rats under three conditions: (1) at "rest," (2) when energy demand is inncreased markedly by seizures, and (3) during total cerebral ischemia. We report no differences in cerebral metabolites between NE-depleted and control hemispheres at "rest." In seizures and ischemia, however, the increase in the level of adenosine 3':5'-monophosphate (cyclic AMP) and the breakdown of glycogen were impaired considerably in the NE-depleted cortex. The data suggest that depletion of central NE impairs cerebral glycogenolysis in response to increased energy demands and ischemia. Such impairment may be mediated via a cyclic AMP-related mechanism.
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PMID:Norepinephrine regulation of cerebral glycogen utilization during seizures and ischemia. 627 95

To characterize further the roles of norepinephrine (NE) and cyclic nucleotides in seizure mechanisms, an examination was made of the effects of several drugs purported to depress noradrenergic influence in the CNS on pentylenetetrazol-induced seizure activity and regulation of cyclic AMP levels in the cerebral cortex and hippocampus in mice. Depletion of brain stores of NE with reserpine or treatment of neonatal mice with 6-hydroxy-dopamine decreased seizure latency and/or threshold and diminished seizure-induced accumulation of cyclic AMP in brain. Propranolol, a beta-adrenergic receptor antagonist, and yohimbine, an alpha 2-adrenergic receptor antagonist, had effects qualitatively similar to reserpine and 6-hydroxy-dopamine, but phentolamine, a mixed alpha-adrenergic antagonist, increased seizure threshold and latency and did not reduce the accumulation of cyclic AMP. None of the drugs tested had any consistent effect on the regulation of cyclic GMP levels in brain during seizures. These data are consistent with the hypothesis that cyclic AMP in brain may be mediating an inhibitory influence of NE on seizure activity.
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PMID:Relationships between norepinephrine and cyclic nucleotides in brain and seizure activity. 628 57

The objective of the present study was to explore if lesions of the ascending noradrenergic pathways, originating in the locus coeruleus, modulate the cerebral metabolic response to bicuculline-induced seizures in rats. Bilateral noradrenergic lesions were performed by 6-hydroxydopamine injections in the caudal mesencephalon, 12-22 days before seizures were induced in animals ventilated on N2O:O2 (75:25). After 5 min of seizures the brain was frozen in situ and cerebral cortex and hippocampus were sampled for analysis. Labile phosphates, glycolytic metabolites, cyclic nucleotides, and free fatty acids were measured. In another series, lesioned animals were used for measurements of cerebral oxygen consumption. The noradrenergic lesions neither modified the electroencephalographically recorded seizure discharge, nor did they alter cerebral oxygen consumption or cerebral energy state. However, when compared to sham-operated animals, those with noradrenergic lesions had significantly higher (115% and 68%) glycogen concentrations and lower (50% and 52%) cyclic AMP concentrations in cerebral cortex and hippocampus, respectively, demonstrating the marked influence of noradrenergic activity on adenylate cyclase activity and glycogenolysis. The lesions failed to modulate the rise in free fatty acids in the cerebral cortex, or the cyclic GMP concentrations in the cerebral cortex and hippocampus. Thus, increased noradrenergic activity during status epilepticus does not seem responsible for lipolysis or for activation of guanylate cyclase.
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PMID:Influence of lesions of the noradrenergic locus coeruleus system on the cerebral metabolic response to bicuculline-induced seizures. 630 1

To elucidate the intracellular mechanism of the bursting activity which is characteristic of seizure discharge, the behavior of the intracellular cyclic nucleotide and the intracellular calcium during pentylenetetrazole (PTZ)-induced bursting activity in snail neurons was investigated. Cyclic AMP was increased about 3-fold by the incubation of ganglia with PTZ. The effect of PTZ on phosphodiesterase activity measured using either cyclic AMP or cyclic GMP as substrate showed a slight increase in cyclic AMP phosphodiesterase activity. The release of calcium from the lysosome fraction was increased by the incubation of ganglia with dibutyryl cyclic AMP. Protein kinase activity was stimulated by the incubation of ganglia with PTZ. Adenylate cyclase activity was stimulated by the incubation of ganglia with PTZ. These findings suggest that PTZ-induced bursting activity in snail neurons is initiated by an intracellular increase of cyclic AMP, which promotes calcium release from lysosomes and induces protein kinase activation.
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PMID:Behavior of intracellular cyclic nucleotide and calcium in pentylenetetrazole-induced bursting activity in snail neurons. 630 20

A microinjection of ferric chloride solution into the left frontal cortex of rats induced epileptic discharges which were recorded by electrocorticography. In animals having such electrographic seizure activity 30 to 60 days after the injection, the accumulation of cyclic AMP elicited by norepinephrine was examined in slices from four cortical regions. The accumulation was significantly greater in the left anterior area, into which region the ferric chloride solution was injected, than in the right anterior area. There was also a tendency for greater norepinephrine-elicited accumulation of cyclic AMP to occur in the left posterior area than in the right posterior area.
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PMID:Elicitation of cyclic AMP accumulation by norepinephrine in the iron-induced epileptogenic cerebral cortex of rats. 631 69

The influence of chronic dietary lithium administration and electroconvulsive therapy on adenosine A1 and A2 receptors in rat brain were determined. A2 receptor activity was measured by accumulation of cyclic AMP in a cerebral cortical slice preparation after in vitro addition of 2-chloro-adenosine, and was unchanged in animals which received chronic Li but reduced following chronic ECT. A similar reduction was found in the response to noradrenaline and a combination of the two agents. A1 receptors were measured by binding of [3H]cyclohexyladenosine. Both Kd and Bmax values were unchanged after chronic Li or a single ECS, but chronic ECT led to a 70% increase in Bmax. It is proposed that this effect may mediate the reduced locomotor activity seen after chronic ECT in rats, and that it may also be related to the increase in seizure thresholds seen during a course of ECS treatment in humans.
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PMID:The effects of chronic lithium and ECT on A1 and A2 adenosine receptor systems in rat brain. 632 Sep 53

The concentrations of cyclic 3', 5'-guanosine monophosphate (cGMP) and cyclic 3', 5'-adenosine monophosphate (cAMP) in the cerebellar and cerebral cortex were measured during lidocaine infusion and during bicuculline-induced seizures in rats. The rats were divided into three groups: control, lidocaine (0.74 mg/min) and bicuculline (1.2 mg/kg). The lidocaine group was divided into four stages according to the EEG pattern; desynchronized, synchronized, seizure and recovery. At the desynchronized and synchronized stages, cGMP and cAMP concentrations in both cerebellar and cerebral cortex remained unchanged except for a modest decrease in cerebral cGMP at the desynchronized stage. At the seizure stage, cerebellar cGMP increased from 5.2 +/- 0.9 to 9.2 +/- 1.4 pmol/mg protein and cerebellar cAMP decreased from 8.9 +/- 0.6 to 6.9 +/- 0.6 pmol/mg protein. These changes in concentrations at the seizure stage returned to the control at the recovery stage. During bicuculline-induced seizures, cGMP and cAMP concentrations increased strikingly in both cerebellar and cerebral cortex. These results indicated that lidocaine-induced seizures were accompanied by significant changes in cerebellar cyclic nucleotide concentrations in rats.
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PMID:Cyclic nucleotides in rat brain during lidocaine infusion. 632 23


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