The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduces the delayed neuronal damage due to forebrain ischemia in rats.
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 degrees 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.[1]References
- The selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reduces the delayed neuronal damage due to forebrain ischemia in rats. Nanri, K., Montécot, C., Springhetti, V., Seylaz, J., Pinard, E. Stroke (1998) [Pubmed]
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