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