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Involvement of platelet-activating factor in glutamate-induced neurotoxicity

Involvement of platelet-activating factor in glutamate-induced neurotoxicity
血小板活化因子参与谷氨酸诱导的神经毒性
批准号:
12671344
负责人:
HIRASHIMA Yutaka
金额:
$1.79万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2000
资助国家:
日本
项目状态:
已结题
起止时间:
2000 至 2002

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中文摘要
翻译
我们使用腺病毒载体,在培养的大鼠神经元中诱导了血浆型血小板激活因子乙酰水解酶(PAF乙酰水解酶)的过度表达。过度表达该酶的神经元在谷氨酸诱导的损伤中有所减轻,主要表现为细胞凋亡减少。我们观察到这种酶可以减少脂质过氧化和保护线粒体功能,这可能是我们观察到的抵抗谷氨酸诱导的神经元损伤的基础。观察了新型血小板激活因子受体拮抗剂E5880预防蛛网膜下腔出血(SAH)后脑血管痉挛的有效性和安全性。71例SAH患者在3d内接受了破裂动脉瘤手术。静脉注射E5880(30 0μg或12 0 0μg,每日2次),4天内开始,持续14天。症状性血管痉挛、CT低密度区和血管造影血管痉挛的发生率低于安慰剂…。在以前的研究中有更多的O组。与以前的研究相比,临床结果是有利的。未观察到临床上重要的不良反应。这些结果表明,E5880是治疗SAH所致脑血管痉挛的安全有效的药物。应用抗焦虑药物依替唑仑对血肿摘除后慢性硬膜下血肿(CSH)患者进行治疗,并与未用药的对照组进行比较。脑部计算机断层扫描显示硬膜下血肿的剩余体积在切除后大约1个月被测量。依替唑仑组的体积明显小于对照组。术后3个月,依替唑仑组未发现血肿复发,但对照组血肿复发明显增多。使用依替唑仑可能有助于预防CSH的复发。较少
英文摘要
Using an adenoviral vector, we induced overexpression of the plasma type of platelet-activating factor acetylhydrolase (PAFacetylhydrolase) in cultured rat neurons. Neurons overexpressing this enzyme showed a decrease in glutamate-induced injury, mainly, apparent as decreased apoptosis. Reduction of lipid peroxidation by this enzyme and protection of mitochondrial function were demonstrated, and these may be the basis of the resistance to glutamate-induced neuronal injury that we observed.The efficacy and safety of a new platelet-activating factor receptor antagonist, E5880, were investigated for preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) in 71 patients with SAH who underwent surgery for ruptured aneurysms within 3 days. Intravenous E5880 administration (300μg or 1200μg twice daily) was begun within 4 days and continued for 14 days. The incidence of symptomatic vasospasm, low-density area on computed tomography, and angiographic vasospasm was lower than in placeb … More o groups in previous studies. Clinical outcome was favorable compared with previous studies. No clinically important adverse events were observed. These results suggest that E5880 is safe and effective in the treatment of patients with cerebral vasospasm due to SAH.Etizolam, an anti-anxiety agent which is an antagonist of platelet-activating factor (PAF) receptors, was administered to patients with chronic subdural hematoma (CSH) after hematoma removal to assess the effectiveness for preventing recurrence compared with control patients not given the drug after surgery. The remaining volumes of subdural hematomas on brain computed tomography were measured approximately 1 month after removal. Volumes in the etizolam group were significantly smaller than those in the control group. Hematoma recurrence was not detected in the etizolam group 3 months after surgery, but was significantly more frequent in the control group. Etizolam administration may be useful for the prevention of recurrence of CSH. Less
期刊论文(13)
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会议论文
Hirashima Y: "Effect of a platelet-activating factor receptor antagonist E5880, on cerebral vasospasm after anaouyswel subaraelnoid hemorrylege"Neurol Med Chir (Tokyo). 41. 165-176 (2001)
Hirashima Y:“血小板激活因子受体拮抗剂 E5880 对 anaouyswel 蛛网膜下腔出血后脑血管痉挛的影响”Neurol Med Chir(东京)。
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Hirashima Y, Takashima S, Matsumura N, Kurimoto M, Origasa H, Endo S: "Right sylvian fissure subarachnoid hemorrhage has electrocardiographic consequences"Stroke. 32. 2278-2281 (2001)
Hirashima Y、Takashima S、Matsumura N、Kurimoto M、Origasa H、Endo S:“右外侧裂蛛网膜下腔出血具有心电图后果”中风。
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Hirashima Y, et al.: "Transfection of the plasma-type platelet-activating factor acetylhydrolase gene attenuates glutamate-indced apoptosis in caltured rat cortical neurous."Brain Res. 885. 128-132 (2000)
Hirashima Y 等人:“血浆型血小板激活因子乙酰水解酶基因的转染可减弱培养大鼠皮质神经细胞中谷氨酸诱导的细胞凋亡。”Brain Res。
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Hirashima Y.,Ueno H.,Karasawa K,Yokoyama K,Setaka M.,Takaku A: "Transfection of plasma-type platelet-activating factor a cetyl hydrolase gene attenuates glutamate-induced apoptosis in cultured rat cortical neuroas"Brain Res. 885(1). 128-132 (2000)
Hirashima Y.、Ueno H.、Karasawa K、Yokoyama K、Setaka M.、Takaku A:“血浆型血小板激活因子 a 十六烷基水解酶基因的转染可减弱培养的大鼠皮质神经元中谷氨酸诱导的细胞凋亡”Brain Res。
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共 13 条
    Lipid peroxidation and PAFacetylhydrolase activity of cerebrospinal fluid in patients with subarachnoid hemorrhage
    • 批准号:
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    • 项目类别:
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    • 财政年份:
      2008
    • 负责人:
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    • 依托单位:
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