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)

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

Blockade of nitric oxide synthase (NOS) activity in the developing nervous system may protect the brain from hypoxic-ischemic insult. We determined the efficacy in 7 day old rat pups of systemically administered cysteamine in reducing neuronal NOS and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivities and protection of the brain from an hypoxic-ischemic insult. Cysteamine reversibly reduced NOS immunoreactivity at 2 h after an intraperitoneal injection of 200 mg/kg. NADPH-diaphorase histochemical reactivity was reduced after 300 mg/kg but all animals had generalized seizures and succumbed to the hypoxia-ischemia. At lower doses, despite the blockade of NOS immunoreactivity, there was no difference in the number of injured animals compared to controls. These results demonstrate that NOS immunoreactivity does not represent all of NADPH-diaphorase reactivity and that blockade of this activity with cysteamine is not protective.
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PMID:Cysteamine eliminates nitric oxide synthase activity but is not protective to the hypoxic-ischemic neonatal rat brain. 884 8

Adequate, high and deficient dietary levels of zinc (Zn) were compared in seizure-susceptible EL mice with respect to convulsions and to nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive hippocampal neurons. Diaphorase positivity is associated with nitric oxide (NO) production. Convulsive seizures in the EL mice given the various diets did not differ over 1-4 weeks, but convulsions in EL mice given the Zn-deficient diet for 4 weeks were more effectively suppressed by injection of zonisamide (ZNS) (75 mg/kg intraperitoneally) than in mice receiving high- or adequate-Zn diet for the same period. Numbers of NADPH diaphorase-positive neurons in the CA1/CA2 region of the hippocampal formation were significantly higher in mice given the Zn-deficient diet for 4 weeks than in mice fed adequate Zn. Mice receiving the high-Zn diet for the same period had significantly fewer NADPH diaphorase-positive neurons in the subiculum than mice with adequate Zn. These results suggest that Zn deficiency inhibits convulsive seizures of EL mice, and that dietary Zn influences numbers of NO producing neurons in the hippocampal formation.
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PMID:Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase-positive neurons in seizure susceptible EL mouse. 957 68

Generalized tonic-clonic seizures of brain stem origin in rats are associated with acute induction of neuronal Fos in several discrete regions of the brain. One particular site in the dorsal pons shows remarkable Fos induction following generalized tonic seizures induced by maximal electroshock in normal rats or by audiogenic stimulation in genetically epilepsy-prone rats (GEPRs). Although this area shows the most intense Fos induction of any brain area following generalized tonic seizures, its identity has been uncertain. Based on its general location, we hypothesized that this nucleus was either 1) a component of the pedunculopontine tegmentum nucleus-pars compacta (PPTn-pc) or 2) the superior lateral subnucleus of lateral parabrachial area (LPBsl). The present study used Fos-protein immunocytochemistry in combination with the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, cholecystokinin (CCK) immunocytochemistry, and neuronal tract-tracing to determine the identity of this cluster of Fos-immunoreactive neurons in the dorsal pons. Following maximal electroshock seizure (MES), Fos labeling was compared to NADPH diaphorase staining (a marker for cholinergic neurons of the PPTn-pc); retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected into the ventromedial nucleus of the hypothalamus (VMH; to identify the LPBsl) or CCK immunoreactivity (also a marker for LPBsl neurons). Results showed this cluster of Fos immunoreactive (FI) neurons to be closely associated, but not overlapping, with the lateral and most caudal aspect of the PPTn-pc. Alternatively, WGA-HRP retrograde-labeled neurons corresponded precisely with the seizure-induced FI neurons. Additionally, the location of CCK immunoreactive neurons directly overlapped with the FI neurons, although they were not nearly as prevalent. These results demonstrate that the seizure-induced FI neurons in this area are neurons of the LPBsl and not cholinergic neurons of the PPTn-pc. This is the first report of seizure-induced Fos expression specifically localized to the superior lateral subnucleus of the lateral parabrachial area.
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PMID:Expression of Fos in the superior lateral subdivision of the lateral parabrachial (LPBsl) area after generalized tonic seizures in rats. 982 Jul 33

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

Recent evidence suggests an important role for NO in cholinergic models of epilepsy. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), a marker of NO containing neurons, was shown to intensely colocalize with GABA in double-labeling studies performed in the hippocampal formation (exception made for the pyramidal cell layer) (Valtschanoff et al., J Comp Neurol 1993:331:111-121). In this sense, it further characterizes an extremely important cell category due to the relevant involvement of inhibitory systems in the mechanisms of genesis and propagation of seizures. Here, we assessed the histochemistry for NADPHd in the hippocampal complex of chronic pilocarpine-epileptic animals. NADPHd-positive cells were lost in almost every hippocampal subfield in pilocarpine-treated rats. The central portion of the polymorphic layer of the dentate gyrus (hilus) presented one of the highest losses of NADPHd-positive cells (55-79%) in the hippocampus. A significant loss of NADPHd-positive cells was seen in strata oriens, pyramidale, and radiatum CA1, CA2, and CA3 subfields. NADPHd staining in the subicular pyramidal cell layer was not different from that observed in controls. A significant loss of NADPHd-stained cells was observed in entorhinal cortex layers II and III in the epileptic group. For entorhinal cortex layers V and VI, however, results varied from an almost complete tissue destruction to an overexpression of NADPHd-positive cells, as well as an increase in neuropil staining. In summary, loss of NADPHd staining was not uniform throughout the hippocampal formation. There has been a growing support for the notion that GABAergic neurons in the hippocampal formation are not equally sensitive to insults. Our results suggest that, as a marker for a subpopulation of GABAergic neurons, NADPHd helps in further refining the characterization of the different neuronal populations sensitive to epileptic activity.
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PMID:Loss of NADPH diaphorase-positive neurons in the hippocampal formation of chronic pilocarpine-epileptic rats. 1040 44

To investigate nitric oxide production in the brain of the EL mouse, an inbred mutant strain of the ddY mouse that is susceptible to convulsive seizures, we measured whole brain nitric oxide metabolites, and counted the number of nitric oxide-producing cells in the parietal cortex and striatum. Nitric oxide metabolites in the brain and serum were determined by measuring levels of nitrite plus nitrate. Nitric oxide-producing cells were demonstrated histochemically by staining for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. Levels of nitrite plus nitrate in the whole brain were significantly lower than those of the control mice, although levels of nitrite plus nitrate in the serum did not differ between groups. There were significantly fewer NADPH-diaphorase-positive cells in the parietal cortex and striatum of the EL mouse compared to the ddY controls. These results suggest that lower nitric oxide production in the brain may be related to the susceptibility of the EL mouse to convulsive seizures.
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PMID:Nitric oxide production is decreased in the brain of the seizure susceptible EL mouse. 1058 20

We evaluated age-related changes in nitric oxide (NO) production in the brains of EL mice, a strain highly susceptible to seizures. A group of EL(s) mice were tossed up weekly to induce convulsive seizures, while in a nonstimulated EL(ns) group induction of convulsive seizures was avoided. Brain levels of nitrite plus nitrate (NOx) in EL(ns) mice were significantly higher than in nonstimulated mice at 10 days, and also higher than levels at 15 and 50 weeks in either EL(s) or EL(ns) mice. A significantly higher number of NO-producing cells were demonstrated in the hippocampus and parietal cortex by staining for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase in EL(s) mice at the ages of 15 and 50 weeks than in EL(ns) mice at the age of 6 weeks. In EL(ns) mice, significantly fewer neurons showed NADPH-diaphorase staining in the hippocampus, striatum and parietal cortex at the age of 50 weeks than at 6 weeks. The present results suggest that whole-brain NOx levels in EL(ns) and EL(s) mice and numbers of NADPH-diaphorase-positive neurons in EL(ns) mice decreased with aging, while increasing of numbers of such neurons in EL(s) mice were assumed to develop in compensation for reduction in whole-brain NOx levels.
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PMID:Age-related alterations of nitric oxide production in the brains of seizure-susceptible EL mice. 1111 84

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

Nitric oxide (NO) is a short-lived radical, which modulates synaptic plasticity, neuronal oscillations and cerebral blood flow. NOS-containing neurones can be detected anatomically by nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry or by NOS immunohistochemistry. Neuropeptide Y(NPY) is the most abundant peptide in the brain. NPY is connected with several vital functions, such as a feeding behaviour, sexual maturation, regulation of circadian rhythms, body temperature, blood pressure and neuroendocrine secretions. Neuropeptide Y also modulates anxiety-related disorders, limbic epileptic seizures as well as learning and memory processes. The study was performed on 45 Wistar rats of various ages (PO, P4, P7, P10, P14, P21, P30, P60, and P120; P--postnatal day). The free-floating sections were stained with standard immunohistochemistry methods. Thereafter the histological sections were studied using the confocal laser microscope equipped. For 3D reconstruction the image analysis program LaserSharp 2000v. 2.0 (Bio-Rad, UK) was used. We found that in the newborn rat both NOS- and NPY-immunoreactivity was weak. It had been increasing gradually until the 7th day of postnatal life, after that until P14 it was maintained on the similar level, and then the number of immunolabelled cells deceased. The developmental changes concerned cell morphology as well--until the 10th day of life the immunoreactive cells were immature, with round or oval bodies and had only a few fibres. From P14 the cells' morphology became similar to that in adult.
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PMID:Distribution of nitric oxide synthase and neuropeptide Y neurones during the development of the hippocampal formation in the rat. 1272 88


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