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)

Pertussis toxin is known to inhibit G proteins via ADP-ribosylation, and a response to pertussis toxin is presumptive evidence of G protein modulation of the activity being studied. Therefore, in order to test the hypothesis that G protein-mediated mechanisms are involved in the pathogenesis of generalized absence seizures, the effect of pertussis toxin in two pharmacological models of generalized absence seizures in rat was investigated. The experimental absence seizure models used were the gamma-hydroxybutyrate (GHB) model and low dose pentylenetetrazole (PTZ) model in rat. Pretreatment with pertussis toxin administered intracerebroventricularly (i.c.v.) resulted in a significant decrease in duration of seizure in both models. These data suggest that G-protein-mediated mechanisms may be involved in the pathogenesis of the bilaterally synchronous spike wave discharges (SWD) that characterize experimental absence seizures.
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PMID:Evidence for G protein modulation of experimental-generalized absence seizures in rat. 130 Apr 89

To examine the role of GTP-binding proteins in amygdaloid (AM) kindling, pertussis toxin (PTX), which inhibits PTX-sensitive GTP-binding proteins through ADP-ribosylation, was injected into the stimulated AM of fully kindled rats. Intra-AM injections of PTX strongly suppressed kindled seizures. The significant seizure suppression began 2 days after the injection, lasted 4 days, and was due to an increase in afterdischarge threshold. The results suggest that PTX-sensitive GTP-binding proteins in the stimulated site play a significant role in the induction of kindled seizures.
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PMID:Suppression of kindled seizure following intraamygdaloid injection of pertussis toxin in rats. 179 82

Hyperglycemic, but not normoglycemic cats exposed to anoxia develop neurologic signs following reoxygenation including fasciculations, focal and tonic-clonic seizures and coma after a symptom-free period. These symptomatic hyperglycemic cats may develop brain edema and will show diffuse neuronal injury or brain infarction depending on length of survival. Brain mitochondria isolated from symptomatic but not asymptomatic cats have decreased ADP- and uncoupler-stimulated oxygen consumption rates. Since impaired respiration could result from altered electron transport chain function, we measured cytochrome c, b, and aa3 concentrations and the activities of the five electron transfer complexes in isolated brain mitochondria. In symptomatic cats marked alterations were present in particular in complex IV, cytochrome oxidase, with a 57% reduction in activity and a 45% reduction in prosthetic group (cytochrome aa3) concentrations. Less marked reductions in other segments of the chain included 27% and 41% decreases, respectively, in cytochrome c concentrations and in electron transfer complex II, succinate:ubiquinone oxidoreductase activity. Cytochrome b concentrations and complex I, II and V activities were unchanged. Small but significant decreases in cytochrome aa3 concentrations (18%) and cytochrome oxidase activity (20%) were also present in mitochondria from postanoxic hyperglycemic cats prior to appearance of neurologic signs. These results indicate that delayed decreases in the activities of specific electron transfer complexes are correlated with impaired mitochondrial respiration and neurologic deterioration in postanoxic hyperglycemic cats. However, it is presently unclear if these postanoxic brain mitochondrial alterations are primary or secondary events in the development of brain injury.
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PMID:Delayed decreases in specific brain mitochondrial electron transfer complex activities and cytochrome concentrations following anoxia/ischemia. 208 31

We previously demonstrated markedly inhibited brain mitochondrial respiration only in cats that (a) were hyperglycemic at anoxia and (b) had neurologic signs, i.e., fasciculations in tongue or facial muscles or focal seizures following reoxygenation. However, since the relationship between time of onset of mitochondrial dysfunction and neurologic signs was unclear, in the present study we killed postanoxic cats immediately when signs first appeared. Cerebrocortical homogenates and isolated brain mitochondria only from symptomatic cats showed markedly inhibited substrate-, ADP-, and uncoupler-stimulated respiration rates. Cytochrome oxidase activity and cytochrome aa3 concentrations were also markedly reduced in these mitochondria. Since brain mitochondrial function was impaired when neurologic signs first appeared, mitochondrial alterations are an important early organellar change correlated with development of neurologic deterioration following anoxia.
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PMID:Delayed onset of neurologic deterioration following anoxia/ischemia coincides with appearance of impaired brain mitochondrial respiration and decreased cytochrome oxidase activity. 215

Systemic lupus erythematosus (SLE) can produce profound disturbances in the central nervous system, characterized by encephalopathy, focal neurologic deficits, cerebral infarction, psychosis, and seizures. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine the in vivo levels of high-energy phosphates in the central nervous system of 10 patients with SLE and 10 age-matched normal controls. 31P NMR spectroscopy was performed on a 1.5-Tesla unit equipped with a dual-tuned 1H-31P surface coil and a software-directed DRESS (depth resolved surface coil spectroscopy) pulse sequence. This procedure detected ADP, ATP, sugar phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and phosphodiesters in the brain tissue of all study subjects. Levels of ATP in the deep white matter of 10 SLE patients were significantly decreased compared with the levels in 10 normal controls, as quantitated by the ratio of ATP:ATP + ADP (mean +/- SD 0.81 +/- 0.11 versus 0.91 +/- 0.05; P less than 0.02). In a subgroup of 4 patients, PCr levels were decreased to a greater extent than the ATP levels. NMR spectroscopic alterations were not related to obvious anatomic lesions, as determined by standard cranial proton magnetic resonance imaging. In 4 SLE patients with markedly abnormal 31P NMR spectra, treatment with prednisone (80 mg/day) normalized the levels of ATP and PCr. Restoration of a normal 31P profile was accompanied by an obvious improvement in the patients' mental status and clinical symptoms. 31P NMR spectroscopy is a powerful new technique for monitoring high-energy phosphate metabolism, and may be particularly useful for characterizing central nervous system disease in patients with neuropsychiatric SLE.
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PMID:Depletion of high-energy phosphates in the central nervous system of patients with systemic lupus erythematosus, as determined by phosphorus-31 nuclear magnetic resonance spectroscopy. 236 38

Hyper- but not normoglycemic cats exposed to 8 min of anoxia show neurologic signs (fasciculations, myoclonic jerks, seizures) that develop after a symptom-free period. We examined brain mitochondrial function and metabolite concentrations at 0, 1, 3, and 5 h following exposure to anoxia, to correlate biochemical findings with the presence ("symptomatic") or absence ("presymptomatic") of neurologic signs. Brain mitochondria isolated postexposure only from symptomatic cats showed markedly decreased (-50%), state 3 (ADP-stimulated), and uncoupler-stimulated respiration rates with NAD- and FAD-linked substrates. Respiratory control and ADP/oxygen (ADP/O) ratios remained unchanged, indicating, respectively, that coupling and efficiency of ATP synthesis were preserved. Thus, inhibition of electron transport chain function, not phosphorylative activity, may be rate limiting for respiration. During anoxia, hyperglycemic cats showed higher brain lactate levels (26 versus 20 mumol/g), but similar ATP and phosphocreatine concentrations, compared with normoglycemic cats. After exposure, in all animals lactate and phosphocreatine were restored to control levels, whereas ATP remained at 85%. Cats that became symptomatic demonstrated four- to sixfold increases in lactate and 50% reductions in phosphocreatine. At 3 and 5 h postexposure, symptomatic animals showed significant reductions in ATP concentrations. We conclude that although initially asymptomatic, hyperglycemic cats exposed to anoxia undergo a neurologic deterioration over several hours following reoxygenation that is correlated with inhibition of mitochondrial respiration, increases in tissue lactate, and decreases in energy state.
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PMID:Delayed neurologic deterioration following anoxia: brain mitochondrial and metabolic correlates. 256 72

The cerebral blood flow is lower in spontaneously hypertensive rats than in normotensive anaesthetized and mechanically ventilated rats during bicuculline-induced seizures, presumably due to the increase in vascular resistance in the hypertensive rats. This study investigates whether the hypertensive rats develop more severe derangement of the cerebral energy metabolites than normotensive rats because of the reduced cerebral blood flow. After 20 min of continuous seizure activity both normotensive and hypertensive rats had significantly decreased levels of phosphocreatine, ATP and glycogen as well as increased lactate and lactate/pyruvate ratio within the parietal cortex compared to controls. The metabolic disturbances were somewhat less pronounced in the hypertensive rats than in the normotensive rats. Thus, ADP was significantly increased in normotensive rats only and the lactate/pyruvate ratio was higher in the normotensive rats. We conclude that spontaneously hypertensive rats are not more prone than normotensive rats to derangement of cerebral energy metabolites during short term bicuculline-induced seizures and that insufficient blood flow is not the primary cause of the metabolic alterations.
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PMID:Cerebral energy metabolism during bicuculline-induced status epilepticus in spontaneously hypertensive rats. 406 Nov 12

Sustained epileptic seizures were induced in cats by means of penicillin (PCN). After a three hour period tissue from the archicortex was removed, frozen, and extracted for metabolic studies. The concentration of ATP, ADP, AMP, phosphocreatine, glucose, glucose-6-phosphate, pyruvate, lactate, glutamate and aspartate were determined. There was a 50% decrease in phosphocreatine concentration, a slight decrease in the level of ATP and a slight increase in the levels of ADP and AMP. There was a decrease in the total adenine nucleotide and the ATP/ADP and ATP/AMP ratios. The absence of a significant change in adenylate energy charge potential reflects the remarkable ability of the brain to stabilize its energy state even after intense seizure activity. A reflection of increased glycolysis is the presence of decreased glucose (nearly 50%), and increased lactate, concentrations. The metabolic changes observed in the archicortex are comparable to those observed by others in the neocortex, indicating perhaps the relative metabolic uniformity of these two types of cortex.
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PMID:Metabolic changes in the hippocampus after prolonged epileptic discharge. 661 55

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.
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PMID:Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate. 673 1

We analyzed brain tissue in 139 rats for adenosine and its metabolites, inosine and hypoxanthine, during the initial 120 seconds of seizures induced by bicuculline. We also measured ATP, ADP, AMP, phosphocreatine (PCr), and lactate. We divided the rats into four groups by adjustment of their preictal arterial oxygen tension: group I, PaO2 > 200 mm Hg; group II PaO2 = 50 mm Hg; and group III: PaO2 = 100 mm Hg. We treated a fourth group whose PaO2 = 100 mm Hg with phentolamine to block the 44% rise in blood pressure which occurred with the onset of seizures. PaCO2 was maintained between 30 anf 40 mm Hg in all groups. Brain tissue was sampled rapidly after 0, 10, 20, 30, 60, and 120 seconds of seizures by the freeze-blow technique. With normoxia (PaO2 = 100 mm Hg) or hyperoxia (PaO2 > 200 mm Hg), adenosine increased within ten seconds of the onset of seizures and remained elevated even after 120 seconds. Elevations in inosine and hypoxanthine were delayed compared to the increases in adenosine. A reduction in PaO2 (50 mm Hg) or systemic blood pressure during seizures caused a further augmentation in the increase in brain adenosine levels. During the seizure period, transient changes in adenine nucleotides and energy charge were observed, but PCr remained depressed and lactate continued to rise. The rapid and sustained increase in cerebral adenosine levels, temporally paralleling the changes in cerebral blood flow, supports the role for adenosine in the regulation of cerebral blood flow.
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PMID:Changes in brain adenosine during bicuculline-induced seizures in rats. Effects of hypoxia and altered systemic blood pressure. 677 98


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