DOI: 10.1161/01.str.29.6.1248. The Selective Inhibitor of Neuronal Nitric Oxide Synthase, 7-Nitroindazole, Reduces the Delayed Neuronal Damage Due to Forebrain Ischemia in Rats

The Selective Inhibitor of Neuronal Nitric Oxide Synthase, 7-Nitroindazole, Reduces the Delayed Neuronal Damage Due to Forebrain Ischemia in Rats

10.1161/01.str.29.6.1248

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Stroke (276)

Abstract

Background and Purpose —The present study was designed to investigate whether neuronally derived nitric oxide (NO) plays a toxic role in the cascade of cellular events triggered by global cerebral ischemia in rats. Methods —7-Nitroindazole (7-NI) was used as a selective inhibitor of neuronal NO synthase. Global ischemia was induced for 20 minutes in anesthetized rats following the four-vessel occlusion model. Electroencephalogram and brain and body temperatures were continuously monitored. All rats were thermoregulated for the entire duration of anesthesia. 7-NI (25 mg/kg) or its vehicle was given intraperitoneally just after the carotid clamping and again 1 hour later. Rats were randomly divided into four groups: (1) vehicle (n=7); (2) 7-NI (n=7); (3) l -arginine (300 mg/kg IP)+7-NI (n=7); and (4) 7-NI associated with warming to 37°C for 7 hours after disruption of anesthesia to compensate for the decrease in temperature induced by 7-NI (n=9). Seven days after ischemia, hippocampal CA1 damage was evaluated by classic histology. The lesion was scored with the use of a point scale, and the surviving neurons were counted. Results —Lesion scores were significantly lower and neuron counts higher in the two (warmed and unwarmed) groups of rats in which 7-NI was given alone than in vehicle- and l -arginine+7-NI–treated rats. Conclusions —The results indicate that 7-NI was neuroprotective in 20-minute global ischemia in rats and that the neuroprotective effect of 7-NI was mostly due to the blockade of NO synthesis, suggesting that NO released from neurons in ischemic conditions has a deleterious influence on hippocampal pyramidal neurons.

Authors 5

Kazunori Nanri (first)
Céline Montécot (additional)
Véronique Springhetti (additional)
Jacques Seylaz (additional)
Elisabeth Pinard (additional)

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Dates

Type	When
Created	14 years, 2 months ago (June 17, 2011, 4:08 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 6:23 p.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 8:15 a.m.)
Issued	27 years, 3 months ago (June 1, 1998)
Published	27 years, 3 months ago (June 1, 1998)
Published Print	27 years, 3 months ago (June 1, 1998)

Funders 0

None

BibTeX

@article{Nanri_1998, title={The Selective Inhibitor of Neuronal Nitric Oxide Synthase, 7-Nitroindazole, Reduces the Delayed Neuronal Damage Due to Forebrain Ischemia in Rats}, volume={29}, ISSN={1524-4628}, url={http://dx.doi.org/10.1161/01.str.29.6.1248}, DOI={10.1161/01.str.29.6.1248}, number={6}, journal={Stroke}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Nanri, Kazunori and Montécot, Céline and Springhetti, Véronique and Seylaz, Jacques and Pinard, Elisabeth}, year={1998}, month=jun, pages={1248–1254} }

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