Mésenge C, Verrecchia C, Allix M, Boulu R R, Plotkine M
Laboratorie de Pharmacologie, Université René Descartes, Paris, France.
J Neurotrauma. 1996 Jan;13(1):11-6. doi: 10.1089/neu.1996.13.11.
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.
本研究调查了一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）和7-硝基吲唑（7-NI）对小鼠中度闭合性颅脑损伤后24小时神经功能缺损的影响。与赋形剂处理组相比，损伤后不久给予低剂量的L-NAME或7-NI可显著减轻神经功能缺损。L-精氨酸（300mg/kg）未改变神经功能缺损，但与L-NAME和7-NI同时给药时可逆转二者的保护作用。L-NAME和7-NI均有剂量相关效应。当在脑损伤后5、30或60分钟给予L-NAME和7-NI时会产生神经保护作用，但在脑损伤后2小时开始治疗则无此作用，这表明两种药物的治疗窗口期较短。这些结果表明，神经元型一氧化氮合酶合成的一氧化氮在创伤性脑损伤后导致神经功能缺损的早期神经毒性级联反应中起重要作用。
