Involvement of platelet-activating factor in glutamate-induced neurotoxicity
| Project/Area Number |
12671344
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
HIRASHIMA Yutaka Toyama Medical and Pharmaceutical University Faculty of Medecine Associate Professor, 医学部, 助教授 (30135016)
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| Co-Investigator(Kenkyū-buntansha) |
KURIMOTO Masanori Toyama Medical and Pharmaceutical University, University Hospital, Assistant Professor, 附属病院, 講師 (10161770)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2001: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | 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 / apoptosis / anti oxidant / 血小板活性化因子 / アポートシス / 遺伝子導入 |
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| Research Abstract |
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
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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
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Report
(4 results)
Research Products
(13 results)
