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(Stroke. 1998;29:1248-1254.)
© 1998 American Heart Association, Inc.

Original Contributions

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

Kazunori Nanri, MD; Céline Montécot, BSc; Véronique Springhetti, BSc; Jacques Seylaz, PhD; Elisabeth Pinard, PhD

From the Laboratoire de Recherches Cérébrovasculaires, CNRS UPR 646, 1FR6, Université Paris 7, France.

Correspondence to Dr Elisabeth Pinard, Laboratoire de Recherches Cérébrovasculaires, 10 Avenue de Verdun, 75010 Paris, France. E-mail pinard{at}ext.jussieu.fr

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.

Editorial Comment

W. Dalton Dietrich, PhD, Guest Editor

Department of Neurology, University of Miami School of Medicine, Miami, Florida

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