Thrombin mediated cytotoxicity during cerebral ischemia
脑缺血期间凝血酶介导的细胞毒性
基本信息
- 批准号:10327599
- 负责人:
- 金额:$ 32.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-08-15 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We propose a novel and exciting hypothesis—based on literature and our own pilot data—that
neuronal injury stimulates astrocyte activation via thrombin and its receptor PAR-1, and the
resulting astrocyte response to injury yields transmissible paracrine protection of neurons.
Together, neurons, astroctyes, endothelial cells, pericytes, and oligodendroglia comprise the
neurovascular unit, or NVU. Data generated from the several aims will yield insights into the
mechanism for the well-documented phenomenon of pre-conditioning; will provide considerable
insights into the mechanisms of differential vulnerability to cerebral injury; and would likely yield
treatment options for stroke patients. To accomplish the aims, we are creating novel conditional
knock-out mice that will provide research tools to the broader research field. The previous
award, R01 NS075930, covered 8/15/2011 to 03/31/2015 and involved 4 aims. All proposed
work has been completed and published or under review. The data from our prior award has
already influenced stroke care significantly, in the form of two funded clinical trials. However, our
prior data could not fully explain the known differences among the elements of the NVU,
specifically, that astrocytes and endothelial cells tolerate ischemia better than neurons. What is
the mechanism of thrombin-mediated pre-conditioning, and can we relate that mechanism to
other forms of pre- and peri-conditioning? Why does the brain contain prothrombin mRNA and
protein and what purpose could be served by thrombin activation in brain? Could we derive
insights about the response of the brain to injury, and specifically explore the cell-subtype
interactions during injury among astrocytes, neurons, pericytes, oligodendroglia, and endothelial
cells? To answer these questions, and to address the central hypothesis of the present award
application, we added significant new models to our repertoire, and generated pilot data
speaking to the feasibility and novelty of the proposed new specific aims.
基于文献和我们自己的试验数据,我们提出了一个新颖而令人兴奋的假设
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Current Advances in the Use of Therapeutic Hypothermia.
低温治疗应用的最新进展。
- DOI:10.1089/ther.2019.29070.jjl
- 发表时间:2020
- 期刊:
- 影响因子:1.2
- 作者:Lundbye,Justin;Badjatia,Neeraj;Polderman,KeesH;Lyden,Patrick
- 通讯作者:Lyden,Patrick
Direct thrombin inhibitor argatroban reduces stroke damage in 2 different models.
- DOI:10.1161/strokeaha.113.004488
- 发表时间:2014-03
- 期刊:
- 影响因子:8.3
- 作者:Lyden P;Pereira B;Chen B;Zhao L;Lamb J;Lei IF;Rajput P
- 通讯作者:Rajput P
Missing outcome data management in acute stroke trials testing iv thrombolytics. Is there risk of bias?
测试静脉溶栓剂的急性卒中试验中缺失结果数据管理。
- DOI:10.1177/2396987320905457
- 发表时间:2020
- 期刊:
- 影响因子:6.1
- 作者:Fernandez-Ferro,Jose;Schwamm,LeeH;Descalzo,MiguelA;MacIsaac,Rachael;Lyden,PatrickD;Lees,KennedyR
- 通讯作者:Lees,KennedyR
Protease activated receptor-1 mediates cytotoxicity during ischemia using in vivo and in vitro models.
- DOI:10.1016/j.neuroscience.2014.09.038
- 发表时间:2014-12-05
- 期刊:
- 影响因子:3.3
- 作者:Rajput, P. S.;Lyden, P. D.;Chen, B.;Lamb, J. A.;Pereira, B.;Lamb, A.;Zhao, L.;Lei, I. -F.;Bai, J.
- 通讯作者:Bai, J.
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Patrick D Lyden其他文献
Patrick D Lyden的其他文献
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{{ truncateString('Patrick D Lyden', 18)}}的其他基金
ZZ-3K3A-301: A multicenter, randomized, placebo-controlled, double-blinded, Phase 3 study to evaluate the efficacy and safety of 3K3A-APC (RHAPSODY-2)
ZZ-3K3A-301:一项多中心、随机、安慰剂对照、双盲、3 期研究,旨在评估 3K3A-APC (RHAPSODY-2) 的有效性和安全性
- 批准号:
10305528 - 财政年份:2022
- 资助金额:
$ 32.39万 - 项目类别:
ZZ-3K3A-201: Safety evaluation of 3K3A-APC in ischemic stroke
ZZ-3K3A-201:3K3A-APC在缺血性中风中的安全性评价
- 批准号:
9095477 - 财政年份:2014
- 资助金额:
$ 32.39万 - 项目类别:
ZZ-3K3A-201: Safety evaluation of 3K3A-APC in ischemic stroke
ZZ-3K3A-201:3K3A-APC在缺血性中风中的安全性评价
- 批准号:
8760276 - 财政年份:2014
- 资助金额:
$ 32.39万 - 项目类别:
ZZ-3K3A-201: Safety evaluation of 3K3A-APC in ischemic stroke
ZZ-3K3A-201:3K3A-APC在缺血性中风中的安全性评价
- 批准号:
8880302 - 财政年份:2014
- 资助金额:
$ 32.39万 - 项目类别:
Thrombin mediated cytotoxicity during cerebral ischemia
脑缺血期间凝血酶介导的细胞毒性
- 批准号:
9927678 - 财政年份:2011
- 资助金额:
$ 32.39万 - 项目类别:
Thrombin Mediated Cytotoxicity during Cerebral Ischemia
脑缺血期间凝血酶介导的细胞毒性
- 批准号:
8318076 - 财政年份:2011
- 资助金额:
$ 32.39万 - 项目类别:
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