Reduction of the Neurological Deficit in Mice with Traumatic Brain Injury by Nitric Oxide Synthase Inhibitors

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Abstract
This study investigates the effect of the NO synthase inhibitors, NG-nitro l-arginine methyl ester (l-NAME) and 7-nitro indazole (7-NI), on the neurological deficit 24 h after a moderate closed head injury in mice. Low doses of l-NAME or 7-NI given soon after the injury significantly reduced the neurological deficit compared to the vehicle-treated group. l-Arginine (300 mg/kg) did not alter the neurological deficit, but reversed the protective effects of both l-NAME and 7-NI when given at the same time. Both l-NAME and 7-NI had dose-related effects. The neuroprotective effects of l-NAME and 7-NI occurred when the drugs were given 5, 30, or 60 min after brain injury, but not when treatment was begun 2 h after brain injury, suggesting a short therapeutic window for both drugs. These results suggest that NO synthesis by neuronal NO synthase plays an important role in the early neurotoxic cascade leading to neurological deficit following traumatic brain injury.