Neuroprotective efficacy of after focal cerebral ischemia in the mouse and inhibition of cortical nitric oxide synthase

Carreau, Alexandra; Duval, D.; Poignet, H.; Scatton, B.; Vigé, Xavier; Nowicki, Jean-Pierre

doi:10.1016/0014-2999(94)90549-5

Cited by 76 publications

(20 citation statements)

References 38 publications

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“…These reports, along with our data, sug gest that treatment with relatively high doses of NOS inhibitors may enlarge the infarct volume, while more moderate inhibition may be neuropro tective. This is consistent with the recent observa tions of Carreau et al (1994), in which moderate inhibition of NOS (0.1-1.0 mg/kg, administered five times postocclusion) was shown to be neuroprotec-…”

Section: Discussionsupporting

confidence: 92%

Effects of Central Inhibition of Nitric Oxide Synthase on Focal Cerebral Ischemia in Rats

Hamada¹,

Greenberg²,

Croul

et al. 1995

J Cereb Blood Flow Metab

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Summary:We have investigated whether central inhibi tion of nitric oxide synthase (NOS) could modify the tis sue damage of focal cerebral ischemia produced by occlusion of the middle cerebral artery (MCA) in rats. �-Nitro-L-arginine methyl ester (L-NAME) was admin istered intracerebroventricularly at two doses 15 min prior to occlusion of the MCA, as well as 4 and 24 h following occlusion. After the injection of L-NAME, the catalytic activity of the constitutive NOS, considered to be mainly neuronal, was effectively suppressed in the sub cortical gray matter bilaterally, but not in the ischemic territory. Seven days after the MCA occlusion, the brains were evaluated for histopathologic damage. High-dose

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Section: Discussionsupporting

confidence: 92%

Effects of Central Inhibition of Nitric Oxide Synthase on Focal Cerebral Ischemia in Rats

Hamada¹,

Greenberg²,

Croul

et al. 1995

J Cereb Blood Flow Metab

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show abstract

“…but is ineffective at 3 and 10 mg͞kg (29). This bell-shaped dose-response curve, revealing a narrow range of efficacy, is also observed with the nonselective inhibitor L-NA (5,32,33). The reason for this effect is unclear but may be lack of in vivo selectivity for nNOS resulting in a reduction of cerebral blood flow (29).…”

Section: Discussionmentioning

confidence: 82%

BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: A promising neuroprotective strategy

Chabrier

Auguet

Spinnewyn

et al. 1999

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

123

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“…14,36,37 However, intraperitoneal administration of 1 mg/kg L-NA also inhibits brain NOS activity partially (maximum 74%). 38 Hence, the major difference between the 2 inhibitors at the time of reperfusion appears to be the inhibition endothelial NOS (eNOS) by L-NA but not 7-NI, as also indicated by changes in blood pressure (see References 14, 36, and 37).…”

Section: Discussionmentioning

confidence: 99%

Role of Endothelial Nitric Oxide Generation and Peroxynitrite Formation in Reperfusion Injury After Focal Cerebral Ischemia

Gürsoy‐Özdemir

Bolay

Sarıbaş

et al. 2000

Stroke

173

108

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Background and Purpose-Reperfusion injury is one of the factors that unfavorably affects stroke outcome and shortens the window of opportunity for thrombolysis. Surges of nitric oxide (NO) and superoxide generation on reperfusion have been demonstrated. Concomitant generation of these radicals can lead to formation of the strong oxidant peroxynitrite during reperfusion. Methods-We have examined the role of NO generation and peroxynitrite formation on reperfusion injury in a mouse model of middle cerebral artery occlusion (2 hours) and reperfusion (22 hours). The infarct volume was assessed by 2,3,5-triphenyl tetrazolium chloride staining; blood-brain barrier permeability was evaluated by Evans blue extravasation. Nitrotyrosine formation and matrix metalloproteinase-9 expression were detected by immunohistochemistry. Results-Infarct volume was significantly decreased (47%) in animals treated with the nonselective nitric oxide synthase (NOS) inhibitor N -nitro-L-arginine (L-NA) at reperfusion. The specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), given at reperfusion, showed no protection, although preischemic treatment with 7-NI decreased infarct volume by 40%. Interestingly, prereperfusion administration of both NOS inhibitors decreased tyrosine nitration (a marker of peroxynitrite toxicity) in the ischemic area. L-NA treatment also significantly reduced vascular damage, as indicated by decreased Evans blue extravasation and matrix metalloproteinase-9 expression. Conclusions-These data support the hypothesis that in addition to the detrimental action of NO formed by neuronal NOS during ischemia, NO generation at reperfusion plays a significant role in reperfusion injury, possibly through peroxynitrite formation. Contrary to L-NA, failure of 7-NI to protect against reperfusion injury suggests that the source of NO is the cerebrovascular compartment.

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Neuroprotective efficacy of after focal cerebral ischemia in the mouse and inhibition of cortical nitric oxide synthase

Cited by 76 publications

References 38 publications

Effects of Central Inhibition of Nitric Oxide Synthase on Focal Cerebral Ischemia in Rats

Effects of Central Inhibition of Nitric Oxide Synthase on Focal Cerebral Ischemia in Rats

BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: A promising neuroprotective strategy

Role of Endothelial Nitric Oxide Generation and Peroxynitrite Formation in Reperfusion Injury After Focal Cerebral Ischemia

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