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)

NADP+, NADPH and glucose 6-phosphate dehydrogenase were determined in the cerebral cortex of mice exposed to high O2 pressure for 0, 8 and 16 min. These time intervals corresponded to 0, 50 and 100% of the CT50 (the time taken for 50% of the mice to convulse). Cerebral NADP+, NADPH and glucose 6-phosphate dehydrogenase also were determined in O2-exposed mice exhibiting hyperactivity, convulsions, and in mice killed 10s after convulsions. Similar increases in cortical NADP+ and decreases in NADPH were found in mice exposed to 610kPa (6 atm.) of 100% O2 for 0, 50 and 100% of the CT50, during hyperactivity, onset of seizure and 10s after convulsions. The NADP+/NADPH ratio increased approx. 25% at 0% of the CT50, and remained at this increased value at all O2-exposure periods including the hyperactive state, onset of seizure and 10s after convulsions. Identical changes in cerebral NADP+ , NADPH and the NADP+/NADPH ratio were found in mice exposed for 16min to 100% O2 at 100, 350 or 610kPa. No change in cerebral glucose 6-phosphate dehydrogenase was found in mice exposed to 610kPa of 100% O2 during the various stages of O2 toxicity. Only in the 10s post-convulsive group was a statistically significant decrease in glucose 6-phosphate dehydrogenase observed. Disulfiram [bis(diethylthiocarbamoyl) disulphide], an effective O2-protective agent, did not prevent the O2-induced increase in cerebral NADP+ and the NADP+/NADPH ratio, or decrease in NADPH.
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PMID:Cerebral oxidized and reduced nicotinamide-adenine dinucleotide phosphate and glucose 6-phosphate dehydrogenase in mice during exposure to high oxygen pressure. 3 67

A method to monitor extracellular glucose in freely moving rats, based on intracerebral microdialysis coupled to an enzyme reactor is described. The dialysate is continuously mixed with a solution containing the enzymes hexokinase and glucose-6-phosphate dehydrogenase, and the fluorescence of NADPH formed enables the on-line registration of extracellular glucose. The method is applied to monitor changes in extracellular brain glucose during the infusion of glucose, electrically induced seizure, immobilization stress, and repetitive hypoxia. After glucose loading or after seizure, hippocampus dialysate glucose concentration was increased transiently. During immobilization, there was a short-lasting decrease and, thereafter, an increase in the extracellular hippocampus glucose. During repetitive hypoxia in rats with a unilaterally occluded carotid artery, the content of glucose of striatal dialysates followed closely changes in blood pressure. These results illustrate the usefulness of the method in studying changes in brain glucose concentrations under pathological and physiological conditions.
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PMID:On-line monitoring of extracellular brain glucose using microdialysis and a NADPH-linked enzymatic assay. 207 9

This study has investigated the feasibility of calculating the cytoplasmic free [NADP+]/[NADPH] ratio in rat brain. The time course of the change in the substrate ratios of the malate dehydrogenase (decarboxylating) [E.C. 1.1.1.40], NADP+-isocitrate dehydrogenase (decarboxylating) [E.C. 1.1.1.42] and 6-phosphogluconate dehydrogenase (decarboxylating) [E.C. 1.1.1.44] reactions was followed for up to 10 min after a single, unmodified electroconvulsive seizure. From the results it has been concluded that during periods of low flux, the direction and magnitude of the change in the cytoplasmic free [NADP+]/[NADPH] ratio can, in fact, be reasonably determined even though there is some uncertainty in the absolute value of the ratio itself. It is recommended that reliance not be placed on a single enzyme system but that one or both of the other systems also be observed under a given experimental condition to increase confidence in the determination. The results also demonstrate that seizure and anoxia have a far lesser effect on the cytoplasmic free [NADP+]/[NADPH] ratio than on the free [NAD+]/[NADH] ratio in the same compartment. These results suggest that the pathways using the nicotinamide-adenine dinucleotide phosphate system are relatively protected from the rapid fluctuations that seizure and anoxia can produce.
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PMID:The calculation of the cytoplasmic free [NADP+]/[NADPH] ratio in brain: effect of electroconvulsive seizure. 679 9

Purposes of this work were to develop an enzyme system as an in vitro model of the NADPH-dependent component of nitric oxide synthase (NOS) and examine the plausible down-regulation of this system and brain NOS by copper (II)2(3,5-diisopropylsalicylate)4[Cu(II)2(3,5-DIPS)4] as a mechanism accounting for its analgesic, anticonvulsant, and other pharmacological activities. Porcine heart diaphorase (PHD) was found to oxidize 114 microM NADPH with the corresponding reduction of an equivalent amount of 2,6-dichlorophenolindophenol (DCPIP). Addition of Cu(II)2(3,5-DIPS)4 to the reaction mixture decreased the reduction of DCPIP without substantially affecting the oxidation of NADPH. The IC50 for Cu(II)2(3,5-DIPS)4 in inhibiting the reduction of DCPIP was 1.5 microM. Mechanistically, this inhibition of DCPIP reduction was found to be due to the ability of Cu(II)2(3,5-DIPS)4 to serve as a catalytic electron acceptor for reduced PHD, which was enhanced by the presence of a large concentration of DCPIP and inhibited by a large concentration of NADPH. Oxidation of NADPH by PHD in the absence of DCPIP was linearly related to the concentration of Cu(II)2(3,5-DIPS)4 through the concentration range of 5-25 microM Cu(II)2(3,5-DIPS)4 with 50% recovery of NADPH oxidation by PHD at a concentration of 16 microM Cu(II)2(3,5-DIPS)4. Whole rat brain tissue sections incubated in medium containing an NADPH-generating system and nitroblue tetrazolium chloride (NBT) were less intensely stained when Cu(II)2(3,5-DIPS)4 was added to the medium. It is concluded that Cu(II)2(3,5-DIPS)4 serves as an electron acceptor in down-regulating PHD reduction of DCPIP and in down-regulating NOS in brain tissue sections. A decrease in NO synthesis in animal models of seizure, pain, and other disease states with Cu(II)2(3,5-DIPS)4 may account for the anticonvulsant, analgesic, and other pharmacological activities of this complex.
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PMID:Down-regulation of NADPH-diaphorase (nitric oxide synthase) may account for the pharmacological activities of Cu(II)2 (3,5-diisopropylsalicylate)4. 942 75

The distribution and time course of changes of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positivity were studied in immature rats (12 and 25 days old) surviving motor status epilepticus (SE) induced by a high dose of pilocarpine. Motor SE characterized by continuous convulsions was interrupted after 2 h by an injection of clonazepam (0.5 mg/kg or 1 mg/kg in 12- and 25-day-old rats, respectively) in order to reduce mortality. Correlation between electroencephalographic and behavioral seizure activity was confirmed using animals with electrodes implanted bilaterally in the hippocampus and sensorimotor cortex. Brains were examined 2, 6, 13, and 21 days after motor SE using NADPH-diaphorase histochemistry. Two types of changes were found in both age groups: (a) decrease of NADPH-d positivity occurred in both neuropil and cell bodies in piriform, periamygdalar, and entorhinal cortices; and (b) NADPH-d positivity was induced in the cell bodies in the hippocampal fields CA1/2, CA3, and dentate gyrus. These changes were more intense in animals surviving SE at postnatal day 25 than in younger age group, and they peaked 2 days after SE. The changes observed after SE disappeared quickly in 12-day-old rat pups, where only moderate changes could be observed in piriform, periamygdalar, and entorhinal cortices 6 days after SE, whereas the changes in the histochemical positivity persisted in older animals even 21 days after SE.
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PMID:Changes in NADPH-diaphorase positivity induced by status epilepticus in allocortical structures of the immature rat brain. 1021 Jan 66

Changes in neuropeptide Y (NPY) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons in the hippocampus were investigated 5, 10 and 20 days after kainic acid (KA) administration using a double labeling method. The numbers of NADPH-d-positive-only and NPY/NADPH-d-positive neurons decreased in the CA1/2-CA3 regions of the hippocampus, 5, 10 and 20 days after KA administration, however, the number of NPY-positive-only neurons increased in the same regions 5 and 10 days after KA administration. In the dentate gyrus (DG) region of the hippocampus, the numbers of NPY-positive-only, NADPH-d-positive-only and NPY/NADPH-d-positive neurons increased 5 days after KA administration, and 20 days after KA administration, the number of NADPH-d-positive-only neurons decreased to levels similar to or lower than the level of the controls. However, the numbers of NPY/NADPH-d-positive and NPY-positive-only neurons in the DG region 20 days after KA administration remained at control levels. These results indicate that, NADPH-d-positive-only neurons are vulnerable to, and NPY-positive-only neurons are resistant to KA-induced seizures in the whole hippocampus, but that NPY/NADPH-d-positive neurons have different sensitivities in subregions of the hippocampus to KA-induced seizures. In addition, the present findings provide the first statistical and morphological evidence, which demonstrates that NPY-positive-only, NADPH-d-positive-only and NPY/NADPH-d-positive neurons in the hippocampus have different sensitivities to KA-induced seizures.
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PMID:Differential changes in neuropeptide Y and nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in rat hippocampus after kainic acid-induced seizure. 1115 33

Genetic and epigenetic factors may alter the normal development of cerebral cortex, producing laminar and cellular abnormalities and heterotopiae, major causes of juvenile, drug-resistant epilepsy. Experimentally-induced migration disorders provide interesting insights in the mechanisms of the determination of neuronal phenotype and connectivity, of congenital cortical dysgenesis and the pathophysiology of associated neurological disorders, such as epilepsy. We investigated the effects of E14 administration of methylazoxymethanol acetate (MAM), which induces microencephaly by ablating dividing cells. Brains from newborn and adult rats were reacted for NADPH-d and CO histochemistry. Moreover, callosally-projecting neurons were retrogradely labeled with DiI at P9 or with BDA in adults. MAM-treated rats displayed a remarkable reduction in cortical thickness, mainly due to reduction in layer IV and in supragranular layers. Heterotopic nodules appeared in the supragranular layers and in the hippocampus. CO-positive barrels in somatosensory cortex were almost absent. The distribution of NADPH-d-positive neurons was regular, but they were rare in heterotopic nodules. Callosally-projecting neurons displayed abnormal orientation of the apical dendrite and increase in the basal dendritic length. Alterations in the dendritic arborization of pyramidal neurons may be one of the substrates for the increased sensitivity to drugs which induce epileptic seizures in these animals.
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PMID:Experimentally-induced microencephaly: effects on cortical neurons. 1278 21

1. Generalized convulsive seizures can be elicited by a single unilateral microinjection of the cholinergic muscarinic agonist, carbachol, into the specific sites of the thalamus including ventral posterolateral and the reticular thalamic nuclei. The implication of the thalamic specific and reticular neurons is reviewed and discussed. 2. On the basis of the c-fos regional expression and well-known efferent and afferent pathways linking these regions, a neuronal network relating the limbic, thalamo-striatal-cortical, and central autonomic systems, was constructed. 3. The pattern of Fos immunoreactivity associated with long-lasting isocortical vasodilatation elicited by generalized convulsive seizures in anesthetized rat following cholinergic stimulation of the thalamus can be attributed to both the electrocortical activity and the long-lasting increase in cortical blood flow. We propose that the sustained cerebral cortical blood flow response during convulsive epileptic seizures may implicate intracerebral vasodilatory and vasoconstrictory neural mechanisms. Double-labeled NADPH-d and Fos-positive neurons implicated in maintaining the sustained isocortical vasodilatory response were found in the anterior lateral hypothalamic area. Inhibition of these neurons prevented the increase in cortical blood flow despite an increased metabolic demand manifested by the ictal electrocortical activity. 4. Medial temporal lobe atrophy, including hippocampus, amygdala, and parahippocampal gyrus (piriform and entorhinal cortices) are the most common pathology in man. However the origin of medial lobe atrophy remain uncertain. Our results provide evidence that the allocortical microvascular inflammation may be in origin of the neurovascular degenerative processes leading to atrophy.
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PMID:Isocortical hyperemia and allocortical inflammation and atrophy following generalized convulsive seizures of thalamic origin in the rat. 1451 31

The localization of NADPH-diaphorase (NADPH-d), inducible NO-synthase (iNOS) and glial fibrillary acidic protein (GFAP) was studied in the astrocytes of the temporal cortex in rats of Krushinsky-Molodkina strain which are genetically prone to audiogenic seizures. The seizure was evoked by thrice-repeated acoustic stimulation. Wistar rats and acoustically untreated seizure-free Krushinsky-Molodkina rats were used as a control. The foci of brain damage were consistently found in the neocortex of the animals with audiogenic seizures. Epileptic foci, 300-400 microm in diameter, were localized in layers III-V; they were found to consist of the clusters of NADPH-d-positive astrocytes and to be present in both hemispheres. In the foci of cortical damage astrocytes expressed iNOS and an elevated level of GFAP. The number of GFAP-immunopositive astrocytes in the foci of damage was increased by 25-37% compared to the control and to undamaged areas of the cortex. Astrocyte NOS and GFAP induction found in this work, suggests the participation of glia in compensatory NO-dependent mechanisms, that are formed in the damage foci of neocortex during the audiogenic seizures.
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PMID:[Induction of NO-synthase and glial fibrillary acidic protein in astrocytes of the temporal cortex in rats with audiogenic epileptiform reaction]. 1535

We sought to determine whether the extracellular compartment contributed to seizure-induced superoxide (O2*-) production and to determine the role of the NADPH oxidase complex as a source of this O2*- production. The translocation of NADPH oxidase subunits (p47phox, p67phox and rac1) was assessed by immunoblot analysis and NADPH-driven O2*- production was measured using 2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)-8-benzyl-3,7-dihydroimidazo [1,2-alpha] pyrazin-3-one-enhanced chemiluminescence. Kainate-induced status epilepticus resulted in a time-dependent translocation of NADPH oxidase subunits (p47phox, p67phox and rac-1) from hippocampal cytosol to membrane fractions. Hippocampal membrane fractions from kainate-injected rats showed increased NADPH-driven and diphenylene iodonium-sensitive O2*- production in comparison to vehicle-treated rats. The time-course of kainate-induced NADPH oxidase activation coincided with microglial activation in the rat hippocampus. Finally, kainate-induced neuronal damage and membrane oxygen consumption were inhibited in mice overexpressing extracellular superoxide dismutase. These results suggest that seizure activity activates the membrane NADPH oxidase complex resulting in increased formation of O2*-.
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PMID:Activation of NADPH oxidase and extracellular superoxide production in seizure-induced hippocampal damage. 1560 2


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