SOURCES AND EFFECTS OF REACTIVE OXYGEN INTERMEDIATES IN THE BRAIN

实验已经在培养的小胶质细胞和星形胶质细胞上进行 从老鼠和仓鼠的大脑皮层中提取。 我们先前已经 表明激活的大鼠小胶质细胞产生反应性 氧物种（ROS），超氧自由基阴离子，在几个小时后， 刺激和一氧化氮，经过约10小时至几小时的时间后， 天 以前，我们也表明仓鼠小胶质细胞释放 很少或没有一氧化氮。 我们现在已经证明， 小胶质细胞也产生一氧化氮。 我们继续进行这些研究 使用从活检样本中获得的正常人类小胶质细胞，并已 显示这些人类小胶质细胞产生很少或没有一氧化氮。 我们 已经测试了超过24种化学激活剂，包括β-淀粉样蛋白（1- 40)以确定它们中的任何一种是否可以激活仓鼠小胶质细胞， 仓鼠和人类的小胶质细胞都不产生NO。 人类的小胶质细胞只被测试过6种不同的化学物质 以确定这些技术是否会成功 产生一氧化氮 因此，我们现在已经证明，仓鼠 小胶质细胞与人类小胶质细胞相似， 小胶质细胞参与的模型，可能更好地使用 仓鼠而不是老鼠因为酶催化分解 精氨酸转化为尿素和鸟氨酸，我们测试了是否抑制 （+）-S-2-氨基-5-碘乙酰氨基戊酸（AIAP）， 一种酶的抑制剂--一氧化氮酶，可能会产生一氧化氮， 仓鼠小胶质细胞的生产。初步实验。指示 这种抑制作用确实从受刺激仓鼠体内产生了一氧化氮 B103细胞来源于神经母细胞瘤细胞系， 特别是缺乏β-淀粉样蛋白前体蛋白。 细胞 在过氧化氢作为氧化剂的存在下生长 应力 我们目前正在评估这种氧化性的 应力我们计划给这些细胞同样的氧化应激， 添加的β-淀粉样前体蛋白的存在，并确定这是否 是抗氧化剂。

Experiments have been performed on microglia and astrocytes cultured from cerebral cortices of mice and hamsters. We have previously demonstrated that activated rat microglia cells produce the reactive oxygen species (ROS), superoxide radical anion, within a few hours after stimulation and nitric oxide, after a period of about 10 hours to several days. Previously, we have also shown that hamster microglia releases little or no nitric oxide. We have now shown that activated mice microglia also produce nitric oxide. We have continued these studies using normal human microglia, obtained from biopsy samples, and have shown that these human microglia produce little or no nitric oxide. We have tested more than 24 chemical activators including beta-amyloid (1- 40) to determine if any one of them could activate hamster microglia to produce nitric oxide, Neither hamster nor human microglia produce NO. Human microglia have only been tested with 6 different chemical activators to determine if any of these would be successful techniques for producing nitric oxide. Thus, we have now shown that hamster microglia are similar to human microglia, and that for animal disease models in which microglia participate, it might be better to use hamsters instead of rats and mice. Since arginase catalyses the breakdown of arginine into urea and ornithine, we tested whether the inhibition of this pathway by (+)-S-2-amino-5-iodoacetamidopentanoic acid (AIAP), an inhibitor of the enzyme, arginase, could possibly produce nitric oxide production in the hamster microglia. Preliminary experiments. indicated that this inhibition did produce nitric oxide from stimulated hamster microglia.The B103 cells, derived from neuroblastoma line, are exceptional in their lack of beta-amyloid precursor protein. The cells have been grown in the presence of hydrogen peroxide as a oxidative stress. We are currently accessing the damage produced by this oxidative stress. We plan to give the same oxidative stress to these cells in the presence of added beta-amyloid precursor protein and determine if this is an antioxidant.