Huang Z, Huang P L, Panahian N, Dalkara T, Fishman M C, Moskowitz M A
Stroke Research Laboratory, Massachusetts General Hospital, Charlestown 02129.
Science. 1994 Sep 23;265(5180):1883-5. doi: 10.1126/science.7522345.
The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform.
一氧化氮（NO）或其反应产物介导脑毒性这一观点仍存在争议，部分原因是使用了非选择性药物来阻断神经元、神经胶质细胞和血管腔室中NO的生成。在神经元型一氧化氮合酶（NOS）活性缺乏的突变小鼠中，大脑中动脉闭塞后24小时和72小时梗死体积显著减小，且神经功能缺损比正常小鼠轻。这一结果不能用血流或血管解剖结构的差异来解释。然而，给予硝基-L-精氨酸抑制内皮型NOS后，突变小鼠的梗死面积变大。因此，神经元产生的NO似乎会加剧急性缺血性损伤，而血管产生的NO在大脑中动脉闭塞后具有保护作用。这些数据强调了开发神经元亚型选择性抑制剂的重要性。
