Estimation of oxygen delivery during cerebral ischemia and the consequent tissue damage.

估计脑缺血期间的氧输送和随之而来的组织损伤。

• 批准号: 05454421
• 负责人: ARAI Toshiyuki
• 金额: $ 4.42万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454421/
• 关键词: cerebral ischemia; gerbils; NIR; MRI; MAP2; oxygen free radicals; EPR; neopterin; ビオプテリン; HPX-XOD反応系; 好中球刺激系; ネオプテリン抗体; 砂ネズミ虚血脳切片; 酸化型ヘモグロビン

Oxygen delivery during cerebral ischemia was estimated using a near infrared laser spectrophotometry (NIR) and magnetic resonace imaging (MRI). The consequent tissue damage and its attenuation by drugs were examined using an immunohistochemical technique (MAP2 stain).1. Oxygen delivery during cerebral ischemia : Cerebral ischemia was produced in a gerbil by occluding the bilateral common carotid arteries for 8 min. Oxygen delivery to brain reduced dramatically during ischemia, which was confirmed by NIR and MRI.2. Tissue damage following cerebral ischemia : Seven days after the above-mentioned ischemic challenge, the gerbils were perfused by a fixative. The brain was removed and its slices were stained by MAP2. Ischemic legions were clealy detected in the CA1 region of both hippocampi.3. Effects of neopterin (NP) on ischemic neuronal damages : The preischemic administration of NP (3mg/kg) attenuated ischemic neuronal damages in gerbils. NP may prevent the ischemic injury by detoxicating oxygen free radicals generated during ischemia-reperfusion.4. Mechanism of oxygen free radical scavenging by neopterin (NP) : In the hypoxanthine-xanthine oxidase and the neutrophil-phorbol myristate acetate reaction systems, the oxygen free radical scavenging activity of NP was examined using an electron paramagnetic resonance (EPR). The results indicated that NPH-4 (the reduced form of NP) detoxicated the generated oxygen free radicals in the both systems, while NP itself suppressed the oxygen free radical generation.

采用近红外激光分光光度法（NIR）和磁共振成像（MRI）评估脑缺血时的氧输送。采用免疫组化技术（MAP 2染色）检测随后的组织损伤及其药物衰减.脑缺血时的氧输送：通过阻断双侧颈总动脉8分钟在沙土鼠中产生脑缺血。缺血期间向脑的氧输送急剧减少，这通过NIR和MRI证实。脑缺血后的组织损伤：在上述缺血激发后7天，用固定剂灌注沙鼠。取出脑，并将其切片用MAP 2染色。双侧海马CA 1区可见明显的缺血灶.新蝶呤（NP）对缺血性神经元损伤的影响：缺血前给予NP（3 mg/kg）可减轻沙土鼠缺血性神经元损伤。NP可能通过清除缺血再灌注过程中产生的氧自由基而起到保护缺血损伤的作用。新蝶呤（NP）清除氧自由基的机理：在次黄嘌呤-黄嘌呤氧化酶和佛波醇-肉豆蔻酸乙酸酯反应体系中，用电子顺磁共振（EPR）方法研究了NP清除氧自由基的活性。结果表明，NPH-4（NP的还原形式）对两种体系中产生的氧自由基具有解毒作用，而NP本身则抑制氧自由基的产生。

项目成果

Toshiyuki Arai: "Effects of neopterin on ischemic neuronal damage in gerbils." Neurosci Lett. 173. 107-110 (1994)

Toshiyuki Arai：“新蝶呤对沙鼠缺血性神经元损伤的影响。”

Arai T.et al.: "Effects of neopterin on ischemic neuronal damage in gerbils." Nurosci Lett. 173. 107-110 (1994)

Arai T.等人：“新蝶呤对沙鼠缺血性神经元损伤的影响。”

Hiroko Mori: "Mechanism of oxygen free radical scavenging by neopterin." FEBS Lett. (in preparation).

Hiroko Mori：“新蝶呤清除氧自由基的机制。”

Hiroko Mori: "Mechanism of oxygen free radical scavenging by neopterin" FEBS Lett. (in preparation).

Hiroko Mori：“新蝶呤清除氧自由基的机制”FEBS Lett。

Shuji Kojima: "Antioxidative activity of 5,6,7,8-tetrahydrobiopterin and its inhibitory effect on the hepatotoxicity induced by paraquat." Free Radical Research. (in press). (1995)

Shuji Kojima：“5,6,7,8-四氢生物蝶呤的抗氧化活性及其对百草枯引起的肝毒性的抑制作用。”