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 effects of new and potent NOS inhibitors, S-methyl-L-thiocitrulline (S-Me-TC), 3-bromo 7-nitro indazole (3-Br-7-NI), and 1-(2-trifluoromethylphenyl) imidazole (TRIM), were examined on the pilocarpine-induced seizures in mice. 3-Br-7-NI and TRIM decreased the frequency of status epilepticus and mortality, while TRIM. In addition, significantly reduced the incidence of seizures. The latencies to onsets of seizures, status epilepticus, and mortality were significantly prolonged by all three NOS inhibitors, while duration of seizures was reduced by 3-Br-7-NI and TRIM. These data suggest an excitatory effect of NO in the neuronal structure involved in the pilocarpine-induced seizures.
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PMID:Anticonvulsant activity of new and potent inhibitors of nitric oxide synthase. 922 32

The effect of acute (120 mg/kg) and chronic (25 mg/kg, twice a day, for 4 days) intraperitonial injection of the nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOARG) was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ) and by sound stimulation of audiogenic seizure-resistant (R) and audiogenic seizure-susceptible (S) rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg) only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg) and protected against PTZ-induced tonic seizures (80 mg/kg). The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure.
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PMID:Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models. 936 27

The short-term efficacy and tolerability of sertraline for adults with pervasive developmental disorders (PDDs) were assessed in this investigation. Forty-two adults with PDDs (autistic disorder, N = 22; Asperger's disorder, N = 6; and PDD not otherwise specified [NOS], N = 14) participated in a 12-week, open-label, systematic trial of sertraline. Behavioral ratings of repetitive symptoms, aggression, and social relatedness were obtained at baseline and after 4, 8, and 12 weeks of sertraline administration. Twenty-four (57%) of 42 patients showed significant improvement, primarily in repetitive and aggressive symptoms. Statistically significant changes in measures of social relatedness did not occur. Patients with autistic disorder and PDD NOS did significantly better than those with Asperger's disorder. Based on global improvement item criteria from the Clinical Global Impression Scale, 15 of 22 (68%) patients with autistic disorder, none of six (0%) patients with Asperger's disorder, and 9 of 14 (64%) patients with PDD NOS were categorized as treatment responders. Sertraline was well tolerated; no adverse cardiovascular effects, extrapyramidal symptoms, or seizures were identified. These findings suggested that sertraline may be an effective treatment for interfering repetitive and aggressive symptoms in adults with PDDs. Definitive statements about the efficacy and tolerability of sertraline for treating adults with PDDs must await results from double-blind, placebo-controlled trials. These preliminary results should not be generalized to include children and adolescents with PDDs.
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PMID:Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation. 947 44

Administration of tacrine (5 mg/kg i.p.), an anticholinesterase agent, in rats pretreated (24 h beforehand) with lithium chloride (LiCl; 12 mEq/kg i.p.) enhances the expression of neuronal nitric oxide (NO) synthase (NOS), increases NO, and causes seizures and hippocampal damage. Here we report immunohistochemistry evidence showing that in rat LiCl and tacrine enhance the expression of cyclooxygenase type 2 (COX-2) enzyme protein in the dorsal hippocampus and elevate brain PGE2 content during the preconvulsive period. The latter effect, but not enhanced COX-2 expression, is inhibited by previous (30 min before tacrine) administration of N omega-nitro-L-arginine-methyl ester (L-NAME; 10 mg/kg i.p.), an inhibitor of NO synthesis, thus implicating NO in the mechanism of stimulation of COX activity leading to elevation of brain PGE2 content. Indomethacin (10 mg/kg given i.p. 30 min before tacrine), an inhibitor of COX activity, prevented brain PGE2 elevation and abolished the expression of seizures and hippocampal damage thus supporting a role for this metabolite of the arachidonic acid cascade in the mechanisms of LiCl and tacrine-evoked neurotoxicity in rat.
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PMID:Systemic administration of N omega-nitro-L-arginine methyl ester and indomethacin reduces the elevation of brain PGE2 content and prevents seizures and hippocampal damage evoked by LiCl and tacrine in rat. 950 Sep 67

The role of nitric oxide (NO) in the pathogenesis of viral encephalitis was investigated by using an experimental model of herpes simplex virus type 1 (HSV-1) encephalitis in Lewis rats. The expression of inducible NO synthase (iNOS) mRNA determined by Northern blotting was observed first in the olfactory bulb and the brain stem on day 5 after intranasal inoculation of HSV-1, and thereafter iNOS mRNA was detected in other brain regions, i.e., cerebrum and cerebellum. In various parts of the brain, excessive NO production was identified by electron spin resonance spectroscopy. The temporal and spatial patterns of iNOS expression coincided with those of viral propagation, as demonstrated by polymerase chain reaction for HSV-1 gene expression as well as by the plaque-forming assay. Immunohistochemical study determined that iNOS was localized mainly in monocyte-derived macrophages. Treatment of virus-infected animals with the NOS inhibitor Nomega-monomethyl-l-arginine (l-NMMA), but not Nomega-monomethyl-d-arginine, significantly ameliorated not only clinical symptoms such as paralysis and seizures but also mortality. Virus yield from brain tissue was not affected by l-NMMA treatment. It is of interest that increased expression of the antioxidant enzyme heme oxygenase-1 was observed in the HSV-1-infected brain; this increased expression was strongly inhibited by l-NMMA treatment. These data suggest that the high level of NO produced by iNOS is a pathogenic factor in HSV-1-induced encephalitis in rats.
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PMID:Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in rats. 1019 Nov 85

Gene therapy is being investigated as a putative treatment option for cardiovascular diseases, including cerebral vasospasm. Because there is presently no information regarding gene transfer to human cerebral arteries, the principal objective of this study was to characterize adenovirus-mediated expression and function of recombinant endothelial nitric oxide synthase (eNOS) gene in human pial arteries. Pial arteries (outer diameter 500 to 1,000 microm) were isolated from 30 patients undergoing temporal lobectomy for intractable seizures and were studied using histologic staining, histochemistry, electron microscopy, and isometric force recording. Gene transfer experiments were performed ex vivo using adenoviral vectors encoding genes for bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVLacZ). In transduced arteries, studied 24 hours after exposure to vectors, expression of recombinant beta-galactosidase and eNOS was detected by histochemistry, localizing mainly to the adventitia (n = 4). Immunoelectron microscopy localized recombinant eNOS in adventitial fibroblasts. During contractions to U46619, bradykinin-induced relaxations were significantly augmented in AdCMVeNOS-transduced rings compared with control and AdCMVLacZ-transduced rings (P < 0.01; n = 6). The NOS inhibitor L-nitroarginine methylester (L-NAME) caused significantly greater contraction in AdCMVeNOS-transduced rings (P < 0.001; n = 4) and inhibited bradykinin-induced relaxations in control and transduced rings (P < 0.001; n = 6). The current findings suggest that in AdCMVeNOS-transduced human pial arteries, expression of recombinant eNOS occurs mainly in adventitial fibroblasts where it augments relaxations to NO-dependent agonists such as bradykinin. Findings from the current study might be beneficial in future clinical applications of gene therapy for the treatment or prevention of cerebral vasospasm.
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PMID:Adenovirus-mediated gene transfer to human cerebral arteries. 1099 58

Shaking behavior, so-called wet dog shakes (WDS), in rats is characteristic behavior indicating morphine abstinence in morphine-dependence and central excitation in relation to seizures elicited by chemicals or electrical stimulation. We have found that paraquat (PQ), a nonselective herbicide, administered systemically to rats induces WDS in a dose-dependent manner. PQ-induced WDS are suppressed by nitric oxide (NO) synthase (NOS) inhibitors, but this suppression is not reversed by an NO precursor, L-arginine (L-Arg). The present study was performed to determine whether the NO system is associated with PQ-induced WDS in rats. A time-course study on the frequency of WDS for each 30-min period up to 120 min after PQ administration (70 mg/kg, s.c.) revealed that significant induction of WDS occurred during the first and second 30-min periods, that is within 60 min of PQ administration. A nonselective NOS inhibitor, Nomega-nitro-L-arginine (L-NA; 30 mg/kg, i.p.), reduced the frequency of the PQ-induced WDS during both of these periods, but the reduced frequency was not reversed by L-Arg (500 mg/kg, i.p.) in either period. Significant induction of WDS occurred when PQ (50 nmol) was administered directly into the ventral or dorsal hippocampus, but not when administered into the amygdala or the caudate putamen, indicating that the hippocampus plays an important role in PQ-induced WDS. The WDS after the administration of PQ into the dorsal hippocampus was significantly suppressed by pretreatment with L-NA (30 mg/kg, i.p.). The extracellular levels of nitrite (NO2-) and nitrate (NO3-), the oxidative products of NO, in the dorsal hippocampus determined by in vivo microdialysis, were stimulated after systemic PQ administration (70 mg/kg, s.c.) in urethane-anesthetized rats. The increases in extracellular NO2- and NO3- were inhibited by L-NA (30 mg/kg, i.p.), and this inhibition was partly reversed by L-Arg (500 mg/kg, i.p.). The increases in extracellular NO2- and NO3- in the dorsal hippocampus appeared 60 min after PQ administration, when the WDS had occurred and disappeared. These findings suggest that NO production in the hippocampus plays a minor role in PQ-induced WDS in rats and that the suppression of PQ-induced WDS by NOS inhibitors might be mediated though complex mechanisms in the brain.
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PMID:No parallel relationship between nitric oxide production and wet dog shakes susceptible to nitric oxide synthase inhibitors following systemic administration of paraquat in rats. 1130 80

Small heat shock proteins have been implicated in playing a role in various cellular processes, including stress-induced cell death. In kainic acid (KA)-treated rat brain, the immunoreactivity of heat-shock protein 27 (HSP27) was markedly increased in glia cells of the limbic system. In the present study, we demonstrated that alpha B-crystallin, a member of the small heat-shock protein family, was strongly induced in reactive astrocytes in hippocampus after KA-induced seizure. The induction was localized mainly in the CA3 region of hippocampus, where massive neuronal loss occurred. We also demonstrated that the delayed induction of alpha B-crystallin and HSP27 immunoreactivities in the hippocampus of epileptic animals was repressed to the levels seen in control animals with preadministration of the selective nNOS inhibitor 7-nitroindazole (7-NI). This repression was reversed by coinjection of L-arginine, a substrate of NOS. Together, these data suggest a role for alpha B-crystallin and HSP27 in reactive gliosis and/or in delayed neuronal death proceeded after KA-induced seizure.
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PMID:Delayed induction of alpha B-crystallin in activated glia cells of hippocampus in kainic acid-treated mouse brain. 1153 26

We examined the effects of 7-nitroindazole (7-NI) and N-omega-nitro-L-arginine methyl ester (L-NAME) on the endogenous nitric oxide (NO) production in vivo, cerebral hemodynamics, and hippocampal lesions to investigate the different roles between endothelial NOS (eNOS) and neuronal NOS (nNOS) during kainic acid (KA)-induced seizures in newborn rabbits. After a pre-treatment with 7-NI (50 mg/kg, i.p.), L-NAME (20 mg/kg, i.v.) or saline (1 ml, i.v.), KA (12 mg/kg, i.v.) was administered. NO production in the brain, regional cerebral blood flow (rCBF), cerebral oxygenation (concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography (EEG) were continuously monitored throughout the experiment lasting at least 60 min after the KA administration. There was a significant increase in NO generation in the brain during KA-induced seizures, which was inhibited by a pre-treatment with 7-NI or L-NAME. KA-induced seizures also increased rCBF significantly, which was inhibited not by 7-NI but by L-NAME. L-NAME pre-treatment caused a significant decrease in HbO2 and a significant increase in HbR during KA-induced seizures, compared with 7-NI and saline pre-treatment. EEG abnormalities and Neuronal damages in the hippocampus were significantly lower in 7-NI- and L-NAME-treated animals respectively, than in saline-treated animals. The present data demonstrated that the selective nNOS inhibitor, 7-NI, attenuated neither rCBF nor cerebral oxygenation during the seizures, while the non-selective NOS (nNOS and eNOS) inhibitor, L-NAME, attenuated both. These findings suggest that NO, probably originating from eNOS, may play an important role in the cerebral circulation. Both 7-NI and L-NAME inhibited the NO production and EEG abnormalities during the seizures that led to less damage to the hippocampus.
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PMID:Different effects between 7-nitroindazole and L-NAME on cerebral hemodynamics and hippocampal lesions during kainic acid-induced seizures in newborn rabbits. 1157 52

Activation of p38 mitogen-activated protein kinase (p38 MAPK) has been implicated in pathological changes in inflammatory and apoptotic processes in various cell types including neurons. Here we report the delayed induction of p38 MAPKs in the brain of mice following kainic acid (KA)-induced seizure. The immunoreactivities of p38alpha and p38beta MAPKs were markedly increased in the brain 4 days after KA administration, especially in the areas undergoing selective neuronal loss. In particular, p38beta was dramatically increased in reactive astrocytes of CA3 and CA1 regions of hippocampus with its enriched localization in the nucleus of astrocytes. The induction of p38beta was sustained for more than 10 days after KA-treatment. Pre-administration of the selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), which suppressed the delayed neuronal death as well as astrogliosis in hippocampus of seizure-experienced animals, dramatically repressed the delayed induction of p38beta MAPK in astrocytes. The repression was reversed by the co-injection with L-arginine (L-arg), a substrate for NOS, which coincided with the aggravation of neuronal death. Together, these data suggested a role of p38 MAPK signal pathway in delayed neuronal death and/or in reactive gliosis in mice with KA-induced seizure.
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PMID:Delayed induction of p38 MAPKs in reactive astrocytes in the brain of mice after KA-induced seizure. 1159 76


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