Effect of NO synthase inhibition on NMDA- and ischaemia-induced hippocampal lesions

Moncada, Claudia; Lekieffre, D.; Arvin, B. Mak; Meldrum, Brian S.

doi:10.1097/00001756-199206000-00020

Cited by 125 publications

(52 citation statements)

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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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“…Lener-Natoli et al (1992) showed that the NOS inhibitors failed to protect hippocampal neurones against NMDA toxicity in diethylether anaesthetized rats. Moncada et al (1992) failed to demonstrate any protective effect of Nw-nitro-Larginine methyl ester (L-NAME) in the ischaemic model. In addition, in a comparative study of the effect of NOS inhibitors, MK-801, and methyl blue (guanylate cyclase inhibitor), Demerle-Pallardy et al (1991) found that, while all these compounds decreased the cyclic GMP levels, only MK-801 was able to reduce neuronal death.…”

Section: Discussionmentioning

confidence: 99%

Effect of l‐arginine/nitric oxide pathway on MPP⁺‐induced cell injury in the striatum of rats

Santiago

Machado

Cano

1994

British J Pharmacology

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1 Protection against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity by two nitric oxide-related compounds, Nw-nitro-L-arginine (L-NOARG) and L-arginine, was studied in the corpus striatum by means of two MPP+ perfusions separated by 24 h. Dopamine extracellular output after the second MPP+ (1, 5 and 10 mM) perfusion was considered as an index of the dopaminergic neurone damage produced by the first MPP+ (1, 5 and 10 mM) perfusion. 2 L-NOARG, systemically administered (10 mg kg-', i.p., every 12 h for 4 days), failed to prevent the neurotoxic action of MPP+ (1 and 10 mM). On the contrary, the neurotoxic effect of MPP+ was increased by L-NOARG administration. 3 L-Arginine (10 mM) perfused 2 h before MPP+ perfusion did not protect against the neurotoxic action of high MPP+ concentrations (5 and 10 mM). At the highest MPP+ concentration used (10 mM), the increase in the extracellular output of dopamine after the second MPP+ perfusion was slower in L-arginine-treated rats than in control and L-NOARG-treated rats. 4 When MPP+ (1 mM) was perfused 2 h after L-arginine (10 mM) perfusion, there was a clear protection against MPP+ neurotoxicity. In the second MPP+ (1 mM) perfusion, the increase in the extracellular output of dopamine in L-arginine-treated rats was twice as high as for the control rats. 5 The results indicate that NO may exert a protective mechanism in the presence of a low ambient redox.

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“…Some reports have portrayed NO as a toxic agent and suggested a role for this agent in mediating neurotoxicity in ischemia reperfusion injury (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Yet, other reports suggest that NO may have a protective effect during ischemia reper- fusion injury (13)(14)(15)(16)(17)(18)30).…”

Section: Discussionmentioning

confidence: 99%

“…Many reports also suggest that during the ischemia reperfusion event, NO mediates tissue injury (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). However, it has been suggested that NO can function as a protective agent on the basis of two lines of evidence: (i) NO synthase (NOS) inhibitors increase tissue damage during in vivo ischemia reperfusion within the cerebral cortex, and (ii) in more direct evidence, NO has been shown to prevent damage during ischemia reperfusion events in both brain and heart (13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.

Wink

Hanbauer

Krishna

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

739

346

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Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells.Nitric oxide, NO, is one of the proposed cytotoxic species produced by the immune surveillance system (1, 2). Many reports also suggest that during the ischemia reperfusion event, NO mediates tissue injury (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). However, it has been suggested that NO can function as a protective agent on the basis of two lines of evidence: (i) NO synthase (NOS) inhibitors increase tissue damage during in vivo ischemia reperfusion within the cerebral cortex, and (ii) in more direct evidence, NO has been shown to prevent damage during ischemia reperfusion events in both brain and heart (13-18). Additional studies provide evidence that NO, though present, plays a minimal role in the pathological effects associated with ischemia reperfusion injury (19,20) or tumor necrosing factor-mediated cytotoxicity (21). Unfortunately, the exact role(s) NO plays in cytotoxicity in vivo is not clear because there are a number of different physiological functions NO or the NOS inhibitors could affect simultaneously. It has been proposed that NO or reactive nitrogen oxide species can directly cause cell death. However, primary neuronal cell cultures exposed to concentrations of NO as high as 1 mM show no adverse effects (22, 23). Many of the biological events in which NO has been proposed as a toxin occur concurrently with the production of reactive oxygen species-e.g., immune response and ischemia reperfusion injury.To clarify the relationship between the cytotoxic properties of the reactive oxygen species and NO, it is necessary to simplify the system. We now show that NO released from a series of compounds known as the "NONOates" (24) Abstract Service Registry Number 136587-13-8) were synthesized and assayed for NO production via chemiluminescence technique as described (24).Enzyme Analysis/Controls. The activity of XO was monitored in the absence and presence of 1 mM DEA/NO by two different assays. (i) Superoxide-induced reduction of ferricytochrome c to ferrocytochrome c was monitored spectrophotometrically at 550 nm (25). The reaction was carried out in a 1-ml volume in aerated 50 mM phosphate buffer (pH 7.8) containing 50 ,AM diethylenetriaminepentaacetic acid. HX was maintained at 2.5 mM and ferricytochrome c at 20 ,uM. The reactions were initiated with the addition of XO (final con...

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Effect of NO synthase inhibition on NMDA- and ischaemia-induced hippocampal lesions

Cited by 125 publications

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Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

Effect of l‐arginine/nitric oxide pathway on MPP⁺‐induced cell injury in the striatum of rats

Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.

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Effect of NO synthase inhibition on NMDA- and ischaemia-induced hippocampal lesions

Cited by 125 publications

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Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

Effect of l‐arginine/nitric oxide pathway on MPP+‐induced cell injury in the striatum of rats

Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.

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Effect of l‐arginine/nitric oxide pathway on MPP⁺‐induced cell injury in the striatum of rats