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: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 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
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671344/
• 关键词: platelet-activating factor; glutamate; PAF acetyl hydrolase; subarachnoid hemorrhage; brain ischemia; chronic subdural hematoma; anti PAF receptor antagonist; 神経細胞; PAFアセチルハイドロレース; アポトーシス; Etizolam; 再発; Adenovirus; PAFacetylhydrolase; neuron

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

使用腺病毒载体，我们诱导过表达的血浆型血小板活化因子乙酰水解酶（PAF乙酰水解酶）在培养的大鼠神经元。过表达这种酶的神经元表现出谷氨酸诱导的损伤减少，主要表现为细胞凋亡减少。证明了这种酶减少脂质过氧化和保护线粒体功能，这些可能是我们观察到的对谷氨酸诱导的神经元损伤的抗性的基础。预防蛛网膜下腔出血（SAH）后脑血管痉挛在71例SAH患者中，这些患者在3天内因破裂的动脉瘤接受了手术。在4天内开始静脉注射E5880（300μg或1200μg，每日两次），并持续14天。症状性血管痉挛、CT低密度区和血管造影性血管痉挛的发生率低于安慰剂组， ...更多信息 o组在以前的研究。与以前的研究相比，临床结果是有利的。未观察到具有临床意义的不良事件。E5880治疗SAH所致脑血管痉挛是安全有效的。慢性硬膜下血肿（CSH）患者在血肿清除后给予血小板活化因子（PAF）受体拮抗剂依替唑仑（Etizolam），以评估其预防复发的有效性，并与术后未给予药物的对照组进行比较。切除后约1个月，测量脑计算机断层扫描显示的硬膜下血肿剩余体积。依替唑仑组的平均动脉压明显小于对照组。术后3个月，依替唑仑组未检测到血肿复发，但对照组明显更频繁。依替唑仑的管理可能是有用的，以防止复发的CSH。少

项目成果

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）。

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。

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。

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。

Hirashima Y, et al.: "Etigolam, an anti-anxiety agant, athennates recurrence of chronic subdural hematoma - Evaluation by comptued tomo graphy -"Neurol Med Chir (Tokyo). 42. 53-56 (2002)

Hirashima Y 等人：“Etigolam，一种抗焦虑剂，可预防慢性硬膜下血肿复发 - 通过计算机断层扫描进行评估 -”Neurol Med Chir（东京）。