Evaluation of focal cerebral ischemia by NMR and histochemistry.

通过核磁共振和组织化学评估局灶性脑缺血。

• 批准号: 09470327
• 负责人: ARAI Toshiyuki
• 金额: $ 8.32万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470327/
• 关键词: focal cerebral ischemia; rat; global brain ischemia; gerbil; nuclear magnetic resonance; lactate; immunohistochemistry; interleukin-1 receptor antagonist; 脳エネルギー代謝; 砂ネズミ全脳虚血; 虚血再潅流障害; 組織化学染色; 遅発性神経細胞死

Effects of neroprotective drugs on cerebral ischemia were evaluated in animals using nuclear magnetic resonance (NMR) and immunohistochemical analyses.1) Focal cerebral ischemia was introduced in spontaneously hypertensive rats (STIR) using a method of intraluminal vascular occlusion. Then, lactate produced in the damaged area was detected by ^1H NMR.spectroscopy. The increase in lactate was larger in transient ischemia than that in permanent one. The increase in lactate in transient ischemia was attenuated by alpha-phenyl-N-tert- butyl nitrone (PBN), a superoxide scavenger.2) Expression of interleukin-1 receptor antagonist (IL- lra) was investigated in rat brain following transient focal cerebral ischemia induced by 30 min of middle cerebral artery occlusion. The expression of IL-lra was observed on the margin of the neuronal damage 1 day after operation, which was enhanced 4 days after operation and withdrawn 7 days after operation.3) Neuroprotective effects of PBN and oxypurinol, a xanthine oxidase inhibitor, were examined in gerbil global brain .ischemia. Ischemic neuronal damage were evaluated one week after a 3.5 mm bilateral carotid artery occlusion by a histochemical analysis (cresyl violet staining). PBN administered 30 min after ischemia partially attenuated the neuronal damage, while oxypurinol did not.These results indicated that the drug effects on focal cerebral ischemia were precisely evaluated using NMR and immunohistochemical analyses.

采用核磁共振（NMR）和免疫组化方法评价神经保护药物对大鼠脑缺血的影响。1)采用腔内血管闭塞法对自发性高血压大鼠（STIR）进行局灶性脑缺血。然后，用^1H核磁共振光谱检测损伤区产生的乳酸。乳酸的增加在短暂性缺血时大于永久性缺血时。超氧化物清除剂- -苯基- n -叔丁基硝基（PBN）可减弱短暂性缺血时乳酸的增加。2)观察脑中动脉闭塞30 min后大鼠脑组织中白细胞介素-1受体拮抗剂（IL- lra）的表达。术后1天观察到IL-lra在神经元损伤边缘的表达，术后4天IL-lra表达增强，术后7天IL-lra表达减弱。3)观察PBN和黄嘌呤氧化酶抑制剂氧嘌呤醇对沙鼠全脑缺血的神经保护作用。在双侧颈动脉闭塞3.5 mm后一周，通过组织化学分析（甲酚紫染色）评估缺血性神经元损伤。缺血30分钟后给予PBN可部分减轻神经元损伤，而氧嘌呤醇则没有。这些结果表明，通过核磁共振和免疫组织化学分析可以准确地评估药物对局灶性脑缺血的影响。

项目成果

Mori H, Arai T, et al.: "Neuroprotective effects of pterin-6-aldehyde in gerbil global brain ischemia : comparison with those of α-phenyl-N-tert-butyl nitrone" Neurosci Lett. 241. 99-102 (1998)

Mori H、Arai T 等人：“蝶呤-6-醛对沙鼠全脑缺血的神经保护作用：与 α-苯基-N-叔丁基硝酮的比较” Neurosci Lett. 241. 99-102 (1998) ）

Arai T,Mori H,Ishii H,Suzuki T,Kojima S,Mori K: "Auto-oxidation of 5,6,7,8-tetrahydroneopterin" Pteridines. 9. 26-28 (1998)

Arai T、Mori H、Ishii H、Suzuki T、Kojima S、Mori K：“5,6,7,8-四氢蝶呤的自动氧化”蝶啶。

Arai T,Mori H^*,et al.: "Auto-oxidation of 5,6,7,8-tetrahydroneopterin." Pteridines. 9. 26-28 (1998)

Arai T、Mori H^* 等人：“5,6,7,8-四氢新蝶呤的自动氧化。”

Mori H, Arai T^*, et al.: "Neuroprotective effects of pterin-6-aldehyde in gerbil global brain ischemia : comparison with those of a-phenyl-N-tert-butyl nitrone." Neurosci Lrtt. (in press). (1998)

Mori H、Arai T^* 等人：“蝶呤-6-醛对沙鼠全脑缺血的神经保护作用：与 a-苯基-N-叔丁基硝酮的比较。”

Arai T, Mori H, et al.: "Oxypurinol, a xanthine oxidase inhibitor and a superoxide scavenger, did tno attenuate ischemic neuronal damage in gerbil" Life Sei. 63. PL107-112 (1998)

Arai T、Mori H 等人：“氧嘌呤醇是一种黄嘌呤氧化酶抑制剂和超氧化物清除剂，并不能减轻沙鼠的缺血性神经元损伤”Life Sei。