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)

Activity-dependent neuroprotective protein (ADNP) is widely distributed in the cytoplasm of neurons and astrocytes of the hippocampus. Kainic acid (KA)-induced seizures increases neuronal nitric oxide synthase (nNOS) in neurons and inducible NOS (iNOS) in glia cells which coincides with a reduction in ADNP in the hippocampus. Inhibitors of NOS or soluble guanylyl cyclase (sGC) activity reduce ADNP under basal conditions in the absence of seizures. Treating animals with these inhibitors prior to KA-induced seizure, in particular, L-NAME (N(G)-nitro-l-arginine methyl ester), advances the onset of the first seizure but reverses the loss of ADNP by 3 days after the first seizure. This suggests that the NO-cGMP pathway has a role in regulating ADNP under both basal physiological conditions and in the pathophysiological changes produced during epileptogenesis.
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PMID:Regulation of activity-dependent neuroprotective protein (ADNP) by the NO-cGMP pathway in the hippocampus during kainic acid-induced seizure. 1837 35

The present study was performed to examine the involvement of nitric oxide (NO) signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol seizure threshold in mice. Minimal dose of pentylenetetrazol (i.v., mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions was recorded as an index of seizure threshold. Adenosine (100 or 200 mg/kg i.p.) produced a significant increase in the seizure threshold for convulsions induced by pentylenetetrazol i.v. infusion. The anti-convulsant effect of adenosine (100 mg/kg i.p.) was prevented by either L-arginine (50 mg/kg i.p.) [substrate for nitric oxide synthase (NOS)] or sodium nitroprusside (3 mg/kg i.p.) [a NO donor]. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg i.p.) [a non-selective NOS inhibitor] or 7-nitroindazole (7-NI) (25 mg/kg i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor] potentiated the anti-convulsant action of sub-effective dose of adenosine (50 mg/kg i.p.). Aminoguanidine (100 mg/kg i.p.) [a specific inducible NOS (iNOS) inhibitor] pre-treatment was not effective in inducing anti-convulsant effect with sub-effective dose of adenosine (50 mg/kg i.p.). Furthermore, the increase in seizure threshold elicited by adenosine (100 mg/kg i.p.) was also inhibited by concomitant administration with sildenafil (5 mg/kg i.p.) [phosphodiesterase 5 inhibitor]. In contrast, treatment of mice with methylene blue (1 mg/kg i.p.) [a direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC)] failed to induce anti-convulsant action with adenosine (50 mg/kg i.p.) against pentylenetetrazol i.v. infusion. The results demonstrated that the anti-convulsant action of adenosine in the pentylenetetrazol i.v. seizure threshold paradigm may possibly involve an interaction with the L-arginine-NO-cGMP pathway which may be secondary to the activation of adenosine receptors.
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PMID:Nitric oxide signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol-induced seizure threshold in mice. 1845 33

Nitric oxide (NO), as a neurotransmitter, exerts various physiological and pathological effects on the brain. Excess NO is toxic to neurons and may cause neuronal apoptosis. However, the cascade of NO-mediated apoptosis is not fully understood. We utilized a recurrent febrile seizures (FS) rat model and found that plasma NO was increased, neuronal apoptosis was evident, the expression of glucose-regulated protein78 (GRP78, a well-established marker of ER stress) was elevated, and caspase-12 (an ER stress-specific proapoptosis molecule) was activated in the hippocampus in a time-dependent manner after recurrent FS. Administration of sodium nitroprusside (SNP, an NO donor) enhanced neuronal apoptosis, down-regulated the expression of GRP78, and increased that of caspase-12 in FS+SNP groups compared with FS groups. In contrast, treatment with N(G)-nitrol-l-arginine methyl ester (l-NAME, a competitive NO synthase inhibitor) inhibited neuronal apoptosis, up-regulated the expression of GRP78, and decreased that of caspase-12 in FS+l-NAME groups compared with FS groups. These results suggest that NO mediates neuronal apoptosis caused by recurrent FS, and that the ER stress pathway is involved in NO-mediated neuronal apoptosis.
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PMID:Nitric oxide-mediated neuronal apoptosis in rats with recurrent febrile seizures through endoplasmic reticulum stress pathway. 1867 83

The possible role of PGs and NO in the development of S&W of DBA/2J mice was investigated by evaluating the effects of dexamethasone, indometacin, mifepristone plus dexamethasone on the S&W, as well as of L-NAME both on the S&W in the electrocorticogram of DBA/2J mice and on morphine- and deltorphin II-induced EEG seizure in rabbits. The results of our data indicate that: a) Both dexamethasone and indometacin (1,10,100 microg/kg/i.p.) reduced the S&W of DBA/2J mice and mifepristone, a glucocorticoid receptor antagonist (1,10,100 microg/kg/i.p.), totally blocked the steroid effect. b) L-NAME (3-300 microg/mouse/ i.c.v.) dose-dependently reduced the S&W of DBA/2J mice whereas D-NAME at the same doses did not affect S&W of mice. The inhibitory effect of L-NAME on S&W of mice was dose-dependently reversed by L-arginine (L-ARG, 3-300 microg/mouse/ i.c.v.) but not by D-arginine. Finally, GTN its own (3-300 microg/mouse/ i.c.v.) significantly increased the S&W of mice and it was also able to reverse the inhibition on S&W of mice operated by L-NAME. c) Morphine and deltorphin II (100 microg/icv/toto) produce EEG seizure activity in rabbits and L-NAME (300 microg/i.c.v./toto), injected 15 min before morphine or deltorphin II, dose dependently prevented the EEG ictal episodes, the spiking activity and the synchronized EEG pattern induced by morphine or deltorphin II. The inhibitory effect of L-NAME on morphine or deltorphin II seizures was dose-dependently reversed by L-arginine (300 microg/icv/toto) but not by D-arginine. Finally, GTN on its own (300 microg/icv/toto) significantly increased morphine or deltorphin II seizures in the rabbit and it was also able to reverse the inhibition on morphine or deltorphin II seizures operated by L-NAME. These results provide a strong evidence that both PGs and NO may play a significant role in the development of brain excitability.
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PMID:The involvement of prostaglandins and nitric oxide in the development of brain excitability: a relationship study. 1885 75

The dentate gyrus (DG) of the normal rat brain contains activity-dependent neuroprotective protein (ADNP) which is widely distributed in the cytoplasm of neurons and astrocytes. Treatment with nitric oxide (NO) synthase (NOS) inhibitor N(G)-nitro-L: -arginine methyl ester (L: -NAME) caused a decrease in ADNP expression in granule cells which persisted 3 days post-treatment. However, treatment with neuronal-specific NOS inhibitor, 7-nitroindazole (7-NI), or soluble guanylyl cyclase inhibitor, ODQ, did not change ADNP expression in the DG. We have previously shown that kainic acid (KA)-induced seizure increases neuronal NOS in neurons and inducible NOS in glia cells and suppresses ADNP in the hippocampus (Cosgrave et al., Neurobiol Dis 30(3):281-292, 2008). In the DG, L: -NAME treatment prior to KA causes ADNP synthesis in granule cells by 3 h which was later restricted to the subgranular zone by 3 days. 7-NI and ODQ had no effect. Double immunostaining for neuronal marker NeuN and ADNP revealed a significant decrease of both ADNP(+) neurons and of total neuron numbers (NeuN(+)) in the hilus of animals having KA-induced seizure that had been pretreated with L: -NAME implying that NO and ADNP may act together to protect hilar neurons. Overall, these observations suggest that NO regulates ADNP in the DG under both basal and pathophysiological conditions.
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PMID:Nitric oxide regulates activity-dependent neuroprotective protein (ADNP) in the dentate gyrus of the rodent model of kainic acid-induced seizure. 1913 Mar 8

Oxygen is a potent cerebral vasoconstrictor, but excessive exposure to hyperbaric oxygen (HBO(2)) can reverse this vasoconstriction by stimulating brain nitric oxide (NO) production, which increases cerebral blood flow (CBF)-a predictor of O(2) convulsions. We tested the hypothesis that phosphodiesterase (PDE)-5 blockers, specifically sildenafil and tadalafil, increase CBF in HBO(2) and accelerate seizure development. To estimate changes in cerebrovascular responses to hyperoxia, CBF was measured by hydrogen clearance in anesthetized rats, either control animals or those pretreated with one of these blockers, with the NO inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME), with the NO donor S-nitroso-N-acetylpenicillamine (SNAP), or with a blocker combined with l-NAME. Animals were exposed to 30% O(2) at 1 atm absolute (ATA) ("air") or to 100% O(2) at 4 or 6 ATA. EEG spikes indicated central nervous system CNS O(2) toxicity. The effects of PDE-5 blockade varied as a positive function of ambient Po(2). In air, CBF did not increase significantly, except after pretreatment with SNAP. However, at 6 ATA O(2), mean values for CBF increased and values for seizure latency decreased, both significantly; pretreatment with l-NAME abolished these effects. Conscious rats treated with sildenafil before HBO(2) were also more susceptible to CNS O(2) toxicity, as demonstrated by significantly shortened convulsive latency. Decreases in regional CBF reflect net vasoconstriction in the brain regions studied, since mean arterial pressures remained constant or increased throughout. Thus PDE-5 blockers oppose the protective vasoconstriction that is the initial response to hyperbaric hyperoxia, decreasing the safety of HBO(2) by hastening onset of CNS O(2) toxicity.
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PMID:Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen. 1917 45

Cannabinoid system plays a pivotal role in the seizure threshold modulation which is mainly mediated through activation of the cannabinoid CB(1) receptor. There is also several evidence of interaction between cannabinoid system and other neurotransmitters including nitric oxide (NO) system. Using model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice, we investigated whether NO is involved in the effects of cannabinoids on the seizure threshold. Injection of the selective cannabinoid CB(1) agonist ACEA (2mg/kg, i.p.) significantly (P<0.01) increased the seizure threshold which was prevented (P<0.001) by pretreatment with the selective CB(1) antagonist AM251 (1mg/kg, i.p.). The NO precursor l-arginine (50 and 100mg/kg, i.p.) potentiated the anticonvulsant effects of the sub-effective dose of ACEA (1mg/kg, i.p.). Pretreatment with non-effective doses of the non-specific NOS inhibitor l-NAME (15 and 30mg/kg, i.p.) and the specific neuronal NOS inhibitor 7-NI (40 and 80mg/kg, i.p.) but not the inducible NOS inhibitor aminoguanidine (10, 50 and 100mg/kg, i.p.) prevented the anticonvulsant effect of ACEA (2mg/kg, i.p.). Co-administration of non-effective dose of AM251 (0.5mg/kg) with both low and per se non-effective doses of l-NAME (1mg/kg, i.p.) and 7-NI (10mg/kg, i.p.) had significant (P<0.01) effect in preventing the anticonvulsant effect of ACEA (2mg/kg, i.p.). Our findings demonstrated that central NO system could be involved in the anticonvulsant properties of the specific cannabinoid CB(1) agonist ACEA, emphasizing on the interaction between two systems in the seizure modulation.
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PMID:Involvement of nitrergic system in the anticonvulsant effect of the cannabinoid CB(1) agonist ACEA in the pentylenetetrazole-induced seizure in mice. 1922 54

In order to assess the role of nitric oxide/cyclicGMP signaling pathway in the anticonvulsant effect of benzodiazepines, we studied the potential interaction of a phosphodiesterase type 5 inhibitor, sildenafil with the effect of diazepam on a mouse model of clonic seizures induced by intravenous infusion of GABA antagonist, pentylenetetrazole (PTZ). Administration of sildenafil (10 mg/kg; per se effective on seizure threshold) could abolish the anticonvulsive effect of diazepam, and a subeffective dose (5 mg/kg), when added to NO precursor L-arginine (50 mg/kg) could cause the same effect. Conversely, subeffective doses of diazepam (0.02 mg/kg) and NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg), administered together, reversed the proconvulsive effect of sildenafil. Our findings indicate that the enhancement of NO/cGMP signaling pathway by sildenafil attenuates the anticonvulsant effect of the benzodiazepine prototype, diazepam. This suggests that the effects of facilitating GABA(A)-mediated inhibition and modulating NO pathways are additive and there might be a role for NO pathway in benzodiazepine effect against PTZ-induced seizures in mice.
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PMID:The interaction of sildenafil with the anticonvulsant effect of diazepam. 1959 87

Pups of Wistar and KM rats (with predisposition to audiogenic epilepsy) were daily injected with neuropeptide semax (50 mg/kg) or NO-synthase inhibitor L-NAME (50 mg/kg) on days 7-11 of life. Alterations of audiogenic seizures pattern were revealed in rats of both strains at the age of 1 month, while changes in seizure severity were genotype-dependent. Both agents enhance neurogenesis in the dentate gyrus of the hippocampus and the delayed effect in the form of altered seizure pattern seems to be determined by this factor. Genotype-dependent alterations of seizure severity after administration of semax and L-NAME were differently directed. These effects are suggested to be underlined by physiological and biochemical mechanisms not related to the intensity of postnatal neurogenesis.
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PMID:Audiogenic epilepsy in mice with different genotypes after neonatal treatments enhancing neurogenesis in dentate gyrus. 1970 48

The role of NO in epileptogenesis has been studied in different experimental models, and the reported results have been highly contradictory. The current study aimed to determine the role of NO in mechanisms of D: ,L: -homocysteine-thiolactone (H) induced seizures by testing the action of L: -arginine (NO precursor) and L: -NAME (NOS inhibitor) on behavioral and electroencephalographic (EEG) manifestations of H-induced seizures. The same holds true with the brain Na(+)/K(+)- and Mg(2+)-ATPase activity in adult male Wistar rats. We showed that the pretreatment with L: -arginine (300, 600 and 800 mg/kg, i.p.) in a dose-dependent manner significantly decreased lethality, seizure incidence and a number of seizure episodes and prolonged latency time to the first seizure elicited by a convulsive dose of H (8 mmol/kg, i.p.). L: -Arginine (800 mg/kg) completely reversed the inhibitory effect of H on the Na(+)/K(+)-ATPase activity in the hippocampus, the cortex and the brain stem and decreased the H-induced spike-and- wave discharges (SWD) formation in EEG. On the other hand, pretreatment with L: -NAME (200, 500 and 700 mg/kg, i.p.) potentiated a subconvulsive dose of H (5.5 mmol/kg, i.p) by increasing incidence and severity determined by a descriptive-rating scale (0-4) and shortening the latency time to the first seizure. The L: -NAME reversed H-induced alterations in the Na(+)/K(+)-ATPase activity in the cortex and the brain stem but not in the hippocampus. At last, the potentiated SWD appearance in EEG and an increased number of lethal outcomes occurred. In the present work, the modulation of NO levels, with the NO precursor and NOS inhibitor, was shed more light on its mechanism of action and answered the question whether NO could be included in the list of anticonvulsant agents in the D: ,L: -homocysteine thiolactone experimental model of seizures in adult rats.
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PMID:The role of nitric oxide in homocysteine thiolactone-induced seizures in adult rats. 1971 60


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