A method for simultaneous measurements of cerebral blood flow and cerebral metabolic rate for oxygen by magnetic resonance imaging.

研究氧的稳定同位素氧-18在缺血再灌注损伤中对氧自由基产生的影响。观察了氧-18对沙土鼠全脑缺血的神经保护作用。结扎双侧颈总动脉5min后1周，用免疫组织化学方法检测微管相关蛋白2(MAP2)的表达。氧-18组在缺血后给予氧-18气体30min，对照组给予普通氧。比较神经元密度，即每1 mm长的CA1区存活神经元的数量，氧-18组与对照组之间没有差异。在本研究中，自旋捕捉剂α-苯基-N-叔丁基硝酮(PBN)的神经保护作用也没有得到证实。由于PBN的治疗效果是众所周知的，从我们的结果很难确定氧-18是否没有神经保护作用。由于计算的复杂性，分子轨道计算没有明显的氧-18的明显特征。另一方面，成功地合成了一种新的自旋自旋剂3，3，5-三甲基-3-苯基-1-吡咯啉-N-氧化物(Ph-M_3PO)，并证明该化合物能有效地清除羟基自由基。此外，还发现黄嘌呤氧化酶抑制剂蝶呤醛具有清除O_2~+的活性。这些新合成和/或发现的自旋捕捉剂和自由基清除剂可以比传统药物更有效地减轻缺血再灌注损伤。

Effects of oxygen-18, a stable isotope of oxygen, on generation of oxygen free radicals in ischemic-reperfusion injury were investigated. Neuroprotective effects of oxygen-18 were examined in gerbil global brain ischemia. Ischemic neuronal damage were evaluated one week after a 5min bilateral carotid artery occlusion by an immunohistochemical reaction for microtubule-associated protein 2 (MAP2). In an oxygen-18 group, oxygen-18 gas was administered for 30min after ischemia, while in a control group, ordinary oxygen was administered. Comparing the neuronal density, i.e.the number of the surviving neurons per 1mm length of the CA1 region, there were no differences between the oxygen-18 and control groups. In the present study, neuroprotective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapper, were not demonstrated, either. Since the therapeutic effects of PBN are well-known, it is difficult to determine whether oxygen-18 has no neuroprotective effects from our results. Molecular orbital calculations did not evident distinctive features of oxygen-18, due to the complication of the calculation. One the other hand, a new spin tapping agent, 3,3,5-trimethyl-3-phenyl-1-pyrroline-N-oxide (Ph-M_3PO) was successfully synthesized, and it was documented that this compound effectively scavenged hydroxyl radicals. Moreover, it was also documented that pterin aldehyde, a xanthine oxidase inhibitor, has O_2^<.->scavenging activity. These newly synthesized and/or discovered spin trappers and free radical scavengers maay attenuate ischemicperfusion injury more effectively than conventional drugs.