Does Nitric Oxide Control Synaptic Zinc Release?
一氧化氮是否控制突触锌的释放?
基本信息
- 批准号:6547753
- 负责人:
- 金额:$ 14.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-07-23 至 2004-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Synaptically-released zinc has toxic impact in seizure, ischemia, and trauma, contributing to neuronal injury in all three conditions. Conversely, blockade of the excitotoxic synaptic zinc flux with zinc chelators can reduce neuronal degeneration markers by as much as 80%. We have recently discovered evidence indicating that Nitric Oxide (NO) may control the synaptic release of zinc. Should NO prove to be the controlling factor, this would open completely new avenues for management of zinc-induced brain damage in stroke, ischemia, trauma, and seizure. Moreover, prophylactic control of the Zn2+ toxicity via NO modulation could be used as therapeutic pretreatment in cardiac bypass and carotid endarterectomy procedures. Our pilot data indicate that NO infused into the brain simultaneously depletes presynaptic boutons of their zinc while releasing zinc into dialysates, and we have complementary data from brain slice preparations indicating that NO causes the release of Zn2+ into the bath. Perhaps more compelling, additional data suggest that zinc-induced neuronal injury after head trauma is decreased by up to 50% after blockade of NO* synthesis. The objective of the present proposal is to establish with certainty whether, in fact, NO controls Zn2+ release during excitotoxicity.
描述(由申请人提供):突触释放的锌在癫痫发作、局部缺血和创伤中具有毒性影响,导致所有三种情况下的神经元损伤。相反,用锌螯合剂阻断兴奋性毒性突触锌通量可以减少多达80%的神经元变性标志物。 我们最近发现的证据表明,一氧化氮(NO)可能控制突触释放的锌。如果NO被证明是控制因素,这将为中风,缺血,创伤和癫痫中锌诱导的脑损伤的管理开辟全新的途径。此外,通过NO调节预防性控制Zn 2+毒性可用作心脏搭桥术和颈动脉内膜切除术的治疗性预处理。 我们的试验数据表明,NO注入大脑的同时耗尽突触前扣的锌,同时释放锌到透析液中,我们有补充数据,从脑切片制备表明,NO导致锌2+释放到浴。也许更令人信服的是,额外的数据表明,锌诱导的神经元损伤后,头部创伤减少了高达50%的NO* 合成阻断后。本建议的目的是确定是否,事实上,NO控制锌2+释放兴奋性毒性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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CHRISTOPHER J. FREDERICKSON其他文献
CHRISTOPHER J. FREDERICKSON的其他文献
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{{ truncateString('CHRISTOPHER J. FREDERICKSON', 18)}}的其他基金
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用于评估儿童和老年人缺锌的便携式仪器
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- 资助金额:
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Portable Instrument For Assessing Zinc Deficiency In Children and The Elderly
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Does Nitric Oxide Control Synaptic Zinc Release?
一氧化氮是否控制突触锌的释放?
- 批准号:
6615666 - 财政年份:2002
- 资助金额:
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