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

一种通过磁共振成像同时测量脑血流量和脑氧代谢率的方法。

• 批准号: 07457356
• 负责人: TOSHIYUKI Arai
• 金额: $ 4.8万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457356/
• 关键词: brain ischemia; ischemic-reperfusion injury; gerbil; oxygen free radicals; spin trapper; PBN; neopterin; mulecular orbital; 脳虚血再潅流; 揮発性神経細胞死; 酸素-18; ph-M_3PO; 分子軌道; 遅発性神経細胞死

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.

本文研究了氧的稳定同位素氧-18对缺血再灌注损伤时氧自由基产生的影响。在沙土鼠全脑缺血模型上观察了氧-18的神经保护作用。采用微管相关蛋白2（MAP 2）免疫组化染色，观察双侧颈总动脉阻断5 min后1周缺血性神经元损伤情况。氧-18组在缺血后给予氧-18气体30 min，而对照组给予普通氧。比较神经元密度，即CA 1区每1 mm长度的存活神经元数量，氧-18组和对照组之间没有差异。在本研究中，α-苯基-N-叔丁基硝酮（PBN），一种自旋捕捉剂，也没有表现出神经保护作用。由于PBN的治疗作用是众所周知的，因此很难从我们的结果确定氧-18是否没有神经保护作用。由于计算复杂，氧-18的分子轨道计算没有明显的特征。另一方面，合成了一种新型的自旋攻丝剂3，3，5-三甲基-3-苯基-1-吡咯啉-N-氧化物（Ph-M_3 PO），并证明该化合物能有效地清除羟自由基。此外，黄嘌呤氧化酶抑制剂蝶呤醛也有清除O_2 ~<.->-的活性。这些新合成和/或发现的自旋捕获剂和自由基清除剂可能比传统药物更有效地减轻缺血再灌注损伤。

项目成果

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Hiroko M 等人：“还原形式的新蝶呤是否可以作为抗氧化剂？”

Watanabe K,et al.: "Pterin-6-aldehyde, an inhibitor of xanthine oxidase, has superoxide anion radical scavenging activity" Biochem Biophys Res Commun.(in press). (1997)

Watanabe K 等人：“Pterin-6-醛，一种黄嘌呤氧化酶抑制剂，具有超氧阴离子自由基清除活性”Biochem Biophys Res Commun.（出版中）。

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Hiroko Mori et al.: "Does the reduced form of neopterin serve as an antioxidant?" Biochem Mol Biol Inter. 40. 799-806 (1996)

Hiroko Mori 等人：“还原形式的新蝶呤是否可以作为抗氧化剂？”