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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of tacrine (5 mg/kg i.p.) in lithium chloride (LiCl; 12 mEq/kg i.p.)-pretreated (24 h beforehand) animals and of kainate (10 mg/kg i.p.) on brain citrulline, the co-product of nitric oxide (NO) synthesis, were studied in rats. High performance liquid chromatography analysis of whole brain tissue homogenates from rats treated with LiCl and tacrine revealed a significant increase in citrulline content before the onset of seizures. This effect was prevented in a stereoselective manner by N omega-nitro-L-arginine methyl ester (10 mg/kg i.p., given 20 min before tacrine), an inhibitor of NO synthase. By contrast, kainic acid (10 mg/kg i.p.) did not affect significantly brain citrulline during the pre-convulsive period. In conclusion, our data indicate that in rats seizures induced by LiCl and tacrine but not kainic acid are triggered by excessive NO production in the brain.
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PMID:Systemic administration of lithium chloride and tacrine but not kainic acid augments citrulline content of rat brain. 878 50

Although a majority of studies suggest that inhibitors of nitric oxide synthase (NOS) are proconvulsant, a substantial minority indicate the opposite (i.e. that inhibitors of NOS are anticonvulsant). As a consequence, the role of endogenous nitric oxide (NO) in the expression of seizures is unclear. In the present series of experiments, we therefore assessed factors governing pro- and anticonvulsant effects of inhibitors of NOS. In mice receiving systemic injections of kainate or picrotoxin, we confirmed the hypothesis that the effects of inhibitors of NOS vary with the model of seizure: Whereas 7-nitroindazole (7-NI) reduced the latency and increased the severity of kainate-induced convulsions (Expt. 1), both 7-NI and N(omega)-nitro-L-arginine methyl ester (L-NAME) slightly delayed clonus following the systemic administration of picrotoxin at doses > or = 3.5 mg/kg but not at doses < or = 3.0 mg/kg (Expts. 2-5). Paradoxically, L-NAME but not 7-NI significantly reduced the CD50 of picrotoxin, which was approximately 2 mg/kg in control mice (Expt. 4), revealing inhibitor-specific interactions with the dose of the convulsant. Finally, we determined in rats that the effects of L-NAME on kainate-induced seizures vary as a function of genetic factors: L-NAME significantly potentiated kainate-induced convulsions in Sprague-Dawley rats but not in Wistar rats (Expt. 6).
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PMID:Factors determining proconvulsant and anticonvulsant effects of inhibitors of nitric oxide synthase in rodents. 879 57

We evaluated the effect of manipulation of nitric oxide (NO) synthesis on epileptiform discharges recorded from immobilized rats during intracerebroventricular injection of alpha-guanidinoglutaric acid (GGA), an endogenous convulsant and a NO synthase (NOS) inhibitor, alone or in combined with a NOS substrate, l-arginine (ARG). GGA alone, or combined with 50 mM ARG, resulted in prolonged electrographical seizures while co-injection of either 100 or 200 mM of ARG with GGA caused significantly protection. These data show that ARG inhibited epileptiform discharges in a dose-dependent fashion, suggesting that the discharges initiated by inhibition of NOS with the intrinsic convulsant GGA are abated by increasing the concentration of the NOS substrate ARG.
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PMID:Seizures induced by alpha-guanidinoglutaric acid, a nitric oxide synthase inhibitor, are controlled by L-arginine. 879 31

1. Mechanisms that regulate the cerebral circulation have been intensively investigated in recent years. The role of several vasodilator mechanisms has been examined in the cerebral circulation, including nitric oxide (NO), trigeminal peptides and potassium channels, as well as the potent vasoconstrictor endothelin. These mediators appear to play a role in physiological and pathophysiological responses of the cerebral circulation. In the present review, we will focus on some recent developments in each of these areas. 2. Nitric oxide is an important regulator of cerebral vascular tone. Tonic production of NO maintains the cerebral vasculature in a dilated state. NO appears to be an important vasodilator during activation of neurons by excitatory amino acids, somatosensory stimulation and cortical spreading depression. Tonic production of NO appears to be critical in vasodilatation during hypercapnia, although NO may not directly mediate vasodilatation. NO produced by immunological NO-synthase appears to be important in dilatation following exposure to bacterial endotoxin. 3. Calcitonin gene-related peptide (CGRP), released from trigeminal perivascular sensory nerves in the brain, is an extremely potent dilator of brain vessels. CGRP may limit noradrenaline-induced constriction of cerebral vessels and contribute to dilatation during hypotension (autoregulation), reactive hyperaemia, seizures and cortical spreading depression. 4. Activation of potassium channels leads to hyperpolarization of cerebral vascular smooth muscle and appears to be a major mechanism for dilatation of cerebral arteries. Agents that increase the intracellular concentration of cyclic 3' 5'-adenosine monophosphate (cAMP) produce vasodilatation in part by activation of large conductance calcium-activated potassium channels (BKCa) and ATP-sensitive potassium channels (KATP). Activation of both KATP and BKCa channels also appears to contribute to vasodilatation during hypoxia. In contrast to KATP channels, BKCa channels appears to be active under basal conditions, contributing to tonic dilatation of cerebral blood vessels. 5. Endothelin is produced in the brain, but its role in the physiological regulation of cerebral blood flow is not known. Endothelin may contribute to the spasm of cerebral arteries following subarachnoid haemorrhage.
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PMID:Recent insights into the regulation of cerebral circulation. 880 May 65

The regulation of neuronal nitric oxide synthase (NOS) mRNA levels during kindling epileptogenesis in the rat brain was investigated using in situ hybridization. Following 40 rapidly recurring seizures evoked by hippocampal stimulations, NOS mRNA expression decreased by 56% in the dentate granule cell layer (maximum at 2 h) and increased by 420,105 and 1260% in the CA1 and CA3 pyramidal layers and piriform cortex, respectively (maximum at 12-24 h). Gene expression had returned to control levels after one week. The presumed alterations of nitric oxide production, following the changes in NOS mRNA shown here, may modulate synaptic function during kindling development, and could influence neuronal vulnerability after epileptic insults.
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PMID:Regulation of neuronal nitric oxide synthase mRNA levels in rat brain by seizure activity. 881 61

The effects of the inhibitors of endothelial and neuronal nitric oxide (NO) synthases, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), respectively, and the precursor of NO, glyceryl trinitrate, on soman-induced seizures, lethality, and neuropathology were studied in rats. It was found that pretreatment of rats with L-NAME and 7-NI potentiated the severity of motor convulsions and enhanced lethality produced by soman. On the other hand, glyceryl trinitrate, administered transdermally at doses ranging from 2.5-5 mg/day 1 day before soman, decreased seizure susceptibility and lethality in soman-intoxicated animals. This was accompanied by a subsequent reduction of central neuronal damage 24 h after soman treatment. Pretreatment with glyceryl trinitrate also reversed seizure latency produced by 7-NI treatment during soman intoxication. These results indicate that neuronal NO may play a prominent role in seizures by acting as an anticonvulsant and neuroprotectant in soman intoxication.
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PMID:The role of nitric oxide in soman-induced seizures, neuropathology, and lethality. 885 97

A potent nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (L-NA), suppressed tonic seizure elicited by pentylenetetrazol (PTZ; 100 mg/kg, SC) in a dose-related manner (25 to 100 mg/kg, IP), but had no effect on clonic seizure. The effect was most potent at 1 h after the administration of L-NA. L-NA (100 mg/kg, IP) suppressed clonic seizure as well as tonic seizure in bicuculline-treated (3.0 or 4.5 mg/kg, SC) mice. However, it did not affect seizures elicited by picrotoxin (2.0 to 6.0 mg/kg, SC). On the other hand, N-methyl-DL-aspartate (NMDLA; 300 mg/kg or 350 mg/kg, IP) induced clonic seizure, but tonic seizure was not always noted. All mice with clonic and tonic seizures died, and some mice with clonic seizure died without accompanying tonic seizure. L-NA did not influence NMDLA-induced seizures, but it appeared to enhance NMDLA lethality, though without statistical significance. These findings suggest distinct roles of NO in seizures induced by different drugs in mice.
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PMID:Distinct effects of N omega-nitro-L-arginine on seizures induced by several drugs in mice. 886 71

1. To investigate the role of nitric oxide in epilepsy we have studied the effects of agents which affect nitric oxide synthesis in sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone (GEP) rats. 2. The neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole (7-NI) is anticonvulsant in these models with ED50 values against clonic seizures in mg kg-1 i.p. (times following injection) of: 74 (+0.25 h), 120 (+1 h) in DAB/2 mice, and 56 (+0.25 h), 42 (+0.5 h), 36 (+1 h), 28 (+2 h), 38 (+4 h), 93 (+8 h) in GEP rats. 3. Therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) for 7-NI are low, ranging from 0.6 to 1.1 at +0.25 h to +1 h after administration in GEP rats, but are more favourable at later times (1.6 at +2 h and 2.9 at +4 h). 4. The substrate for nitric oxide synthase, L-arginine (500-5000 mg kg-1, i.p. or 100-300 micrograms, i.c.v.) but not D-arginine (300 micrograms i.c.v.) is anticonvulsant in DBA/2 mice. L-Arginine (500-5000 mg kg-1, i.p. or 1800-6000 micrograms, i.c.v.) is a more potent anticonvulsant than D-arginine (1500-2500 mg kg-1, i.p. or 6000 micrograms, i.c.v.) in GEP rats. 5. In DBA/2 mice, L-arginine (30 micrograms i.c.v.) reverses the anticonvulsant effect of 7-NI (50 mg kg-1, i.p.). 6. In GEP rats, low dose L-arginine (25-50 mg kg-1, i.p.) but not D-arginine (50 mg kg-1, i.p.) reverses the anticonvulsant effect of low dose 7-NI (25 mg kg-1, i.p.). A higher dose of L-arginine (500 mg kg-1, i.p.) or 7-NI (50 mg kg-1, i.p.) produces summation of anticonvulsant effect. 7. The product for nitric oxide synthase, L-citrulline (250-831 micrograms i.c.v.), is convulsant in DBA/2 mice. 8. The anticonvulsant effect of the neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole, may therefore be mediated by L-arginine accumulation, as well as by a reduction in nitric oxide and L-citrulline formation in rodent models of reflex epilepsy.
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PMID:Anticonvulsant effects of 7-nitroindazole in rodents with reflex epilepsy may result from L-arginine accumulation or a reduction in nitric oxide or L-citrulline formation. 887 70

The number of NADPH diaphorase-positive cells in the CA1/CA2 and CA3 regions of Ammon's horn and the subiculum of the hippocampal formation of EL mice, an inbred mutant strain of the ddY mouse susceptible to convulsive seizures, was fewer than that of ddY mice. These findings suggest that smaller numbers of nitric oxide producing cells in the hippocampal formations of EL mice is related to their susceptibility to convulsive seizures.
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PMID:Sparse distribution of NADPH diaphorase neurons in the hippocampal formation of the inbred mutant strain EL mouse. 888 7

Nitric oxide (NO) is produced by three distinct isoforms of nitric oxide synthases in the central nervous system. Here, the roles of nitric oxide in the central nervous system are reviewed under physiological and pathophysiological conditions. Under physiological conditions, NO plays a role in the regulation of cerebral blood flow and autoregulation, blood flow-metabolism coupling, neurotransmission, memory formation, modulation of neuroendocrine functions, and behavioral activity. Impairment of the NO-mediated cerebrovascular vasodilatation occurs during ischemia-reperfusion, diabetes, hypertension, subararchnoid hemorrhage, and various forms of shock. Enhancement of NO production in the brain occurs during stoke, seizures, and acute and chronic inflammatory and neurodegenerative disorders. The alterations of the expression of the various isoforms of nitric oxide synthases under the above conditions are discussed. Moreover, the molecular mechanisms of NO and peroxynitrite induced cellular injury are delineated. Finally, the current strategies available for selective pharmacological manipulation of individual nitric oxide synthase isoforms are discussed.
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PMID:Physiological and pathophysiological roles of nitric oxide in the central nervous system. 888 82


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