Potentiation of quinolinate-induced hippocampal lesions by inhibition of NO synthesis

Haberny, Kathleen A.; Pou, Sovitj; Eccles, Christine U.

doi:10.1016/0304-3940(92)90074-h

Cited by 67 publications

(17 citation statements)

References 17 publications

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“…Subsequent studies showed that treatment of cultures with low doses of quisqualate, which preferentially kills nitric oxide synthase containing neurons, blocked glutamate neurotoxicity in cultured cortical and striatal neurons (Dawson et al, 1993). These results have been replicated in some studies (Izumi et al, 1992;VigC et al, 1993) but not in others (Demerle-Pallardy et al, 1991;Pauwels and Leysen, 1992;Hewett et al, 1993;Regan et al, 1993;Zinkand et al, 1993;Garthwaite and Garthwaite, 1994) Results in vivo were also inconsistent in protecting hippocampal neurons from NMDA neurotoxicity (Haberny et al, 1992;Lerner-Natoli et al, 1992;Moncada et al, 1992).…”

Section: Discussionmentioning

confidence: 98%

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

et al. 1995

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Nitric oxide may be a key mediator of excitotoxic neuronal injury in the central nervous system. We examined the effects of the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) on excitotoxic striatal lesions. 7-NI significantly attenuated lesions produced by intrastriatal injections of NMDA, but not kainic acid or alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) 7-NI attenuated secondary striatal excitotoxic lesions produced by the succinate dehydrogenase inhibitor malonate, and the protection was reversed by L- arginine but not by D-arginine, 7-NI produced nearly complete protection against striatal lesions produced by systemic administration of 3-nitropropionic acid (3-NP), another succinate dehydrogenase inhibitor, 7-NI protected against malonate induced decreases in ATP, and increases in lactate, as assessed by 1H magnetic resonance spectroscopy. 7-NI had no effects on spontaneous electrophysiologic activity in the striatum in vivo, suggesting that its effects were not mediated by an interaction with excitatory amino acid receptors. 7-NI attenuated increases in hydroxyl radical, 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine generation in vivo, which may be a consequence of peroxynitrite formation. The present results implicate neuronal nitric oxide generation in the pathogenesis of both direct and secondary excitotoxic neuronal injury in vivo. As such they suggest that neuronal nitric oxide synthase inhibitors may be useful in the treatment of neurologic diseases in which excitotoxic mechanisms play a role.

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Section: Discussionmentioning

confidence: 98%

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

et al. 1995

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“…However, the role of eNOS inhibition is still controversial. L-NAME protects hippocampal pyramidal neurons against kainite-induced excitotoxicity in rats (Jones et al, 1998) and in newborn rabbits (Takei et al, 2001), but eNOS inhibition can also aggravate seizures in animal models (Haberny et al, 1992;Starr and Starr, 1993;Penix et al, 1994;Tsuda et al, 1997). For example, L-NAME treatment facilitated pilocarpine-induced seizures (Starr and Starr, 1993) and seizures induced by DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate), an inverse agonist for the GABAA receptor benzodiazepine binding site, in mice (Tsuda et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus

Byun

Lee

Jeon

et al. 2009

Korean J Physiol Pharmacol

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Nitric oxide (NO) has both neuroprotective and neurotoxic effects depending on its concentration and the experimental model. W e tested the effects of NG-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and aminoguanidine, a selective inducible NOS (iNOS) inhibitor, on kainic acid (KA)-induced seizures and hippocampal CA3 neuronal death. L-NAME (50 mg/kg, i.p.) and/or aminoguanidine (200 mg/kg, i.p.) were administered 1 h prior to the intracerebroventricular (i.c.v.) injection of KA. Pretreatment with L-NAME significantly increased KA-induced CA3 neuronal death, iNOS expression, and activation of microglia. However, pretreatment with aminoguanidine significantly suppressed both the KA-induced and L-NAME-aggravated hippocampal CA3 neuronal death with concomitant decreases in iNOS expression and microglial activation. The protective effect of aminoguanidine was maintained for up to 2 weeks. Furthermore, iNOS knockout mice (iNOS − /− ) were resistant to KA-induced neuronal death. The present study demonstrates that aminoguanidine attenuates KA-induced neuronal death, whereas L-NAME aggravates neuronal death, in the CA3 region of the hippocampus, suggesting that NOS isoforms play different roles in KA-induced excitotoxicity.

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“…For example, hippocampal long-term potentiation is inhibited by NMDA antagonists and by NOS inhibitors (O'Dell et al, 1991;Schuman & Madison, 1991). These antagonists have also been found to protect against NMDAinduced neurotoxicity (Haberny et al, 1992;Dawson et al, 1993;Ayata et al, 1997). They also block NMDA-mediated convulsions (Nakamura et al, 1995), and impair learning and memory in several animal models (Ward et al, 1990;Chapman et al, 1992;BoÈ hme et al, 1993;HoÈ lscher & Rose, 1993;HoÈ lscher et al, 1995;Yamada et al, 1995;Harder et al, 1998;Ingram et al, 1998a,b;Meyer et al, 1998;Zou et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Blockade of phencyclidine‐induced effects by a nitric oxide donor

Bujas‐Bobanovic

Bird

Robertson

et al. 2000

British J Pharmacology

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1 Phencyclidine (PCP) is widely used as an animal model of schizophrenia. The aim of this study was to better understand the role of nitric oxide (NO) in the mechanism of action of PCP and to determine whether positive NO modulators may provide a new approach to the treatment of schizophrenia. 2 The eects of the NO donor, sodium nitroprusside (SNP), were studied in PCP-treated rats. Following drug administration, behavioural changes and the expression of c-fos, a metabolic marker of functional pathways in the brain, were simultaneously monitored. 3 Acute PCP (5 mg kg 71 , i.p.) treatment induced a complex behavioural syndrome, consisting of hyperlocomotion, stereotyped behaviours and ataxia. Treatment with SNP (2 ± 6 mg kg 71 , i.p.) by itself produced no eect on any behaviour studied but completely abolished PCP-induced behaviour in a dose-and time-dependent manner. 4 PCP had dierential regional eects on c-fos expression in rat brain, suggesting regionally dierent patterns of neuronal activity. The most prominent immunostaining was observed in the cortical regions. Pre-treatment with SNP blocked PCP-induced c-fos expression at doses similar to those that suppress PCP-induced behavioural eects. 5 These results implicate the NO system in the mechanism of action of PCP. The fact that SNP abolished eects of PCP suggests that drugs targeting the glutamate-NO system may represent a novel approach to the treatment of PCP-induced psychosis and schizophrenia.

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Potentiation of quinolinate-induced hippocampal lesions by inhibition of NO synthesis

Cited by 67 publications

References 17 publications

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus

Blockade of phencyclidine‐induced effects by a nitric oxide donor

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