ACTIVE THROMBOSIS, THROMBOLYSIS, AND STROKE OUTCOME

活动性血栓形成、血栓溶解和中风结果

• 批准号: 6627651
• 负责人: BRANT D WATSON
• 金额: $ 34.55万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627651
• 关键词: antithrombins; brain circulation; cerebral artery; cerebral ischemia /hypoxia; disease /disorder model; enzyme inhibitors; fibrinolysis; fibrinolytic agents; gene expression; in situ hybridization; laboratory rat; lipid peroxides; malonaldehyde; monoclonal antibody; myeloperoxidase; neuropharmacology; nitric oxide synthase; outcomes research; pathologic process; reperfusion; selectins; stainings; stroke; thrombosis; tissue /cell culture; vascular endothelium

DESCRIPTION: Although thrombolysis by plasminogen activators is an accepted acute clinical treatment for stroke there is still a need to evaluate fully, in a relevant animal model, the consequences of the resultant reperfusion for metabolically compromised brain tissue. A reversible model of thrombotic stroke has been developed, in which the ictus is initiated by photochemically mediated (photothrombotic) occlusion of the rat middle cerebral artery, resulting in a fibrin-free platelet thrombus resistant to conventional (rt-PA) thrombolytic treatment. Such thrombi may account for the majority of recanalization failures seen clinically. Reperfusion is then achieve photophysically by a proprietary process that facilitates dethrombosis, evidently by enhanced penetration of antithrombotic plasma factors. For occlusion times less than 2 hr, cortical cerebral blood flow (CBF) is established within 5-30 min, but full flow restoration at later times will likely require thrombin inhibitor (or plasminogen activator) administration to clear stasis-induced distal secondary thrombi. Although tissue recovery is expected to coincide with flow recovery at early times, "reperfusion injury" concomitant with irreversible cellular changes presaging infarction may occur at later times, even if the microcirculation is preserved by antithrombin treatment via inhibition of the expression of P-selectin, which precedes leukocyte stasis. Indicators of developing reperfusion injury such as expression of P-selectin on endothelium and on thrombin-activated platelets, myeloperoxidase activity, and lipid peroxidation byproducts malondialdehyde and 4-hydroxy-2-nonenal will be monitored by immunostaining procedures at times up to 1 day. The effect of reperfusion on endothelial nitric oxide synthase protein and gene expression will be assessed by immunostaining and in situ hybridization. Outcome at 3 days, monitored by histological evaluation of regions of frank and incomplete infarction, will be correlated with the time course of reperfusion-inducing treatments and associated molecular changes.

描述：虽然纤溶酶原激活剂溶栓是公认的

项目成果

Serotonin release into plasma during common carotid artery thrombosis in rats.

大鼠颈总动脉血栓形成期间血清素释放到血浆中。

• DOI: 10.1161/01.str.23.6.870
• 发表时间: 1992
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Wester,P;Dietrich,WD;Prado,R;Watson,BD;Globus,MY
• 通讯作者: Globus,MY

A photothrombotic 'ring' model of rat stroke-in-evolution displaying putative penumbral inversion.

大鼠中风进化的光血栓“环”模型显示假定的半影反转。

• DOI: 10.1161/01.str.26.3.444
• 发表时间: 1995
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Wester,P;Watson,BD;Prado,R;Dietrich,WD
• 通讯作者: Dietrich,WD

A dual role for nitric oxide in NMDA-mediated toxicity in vivo.

一氧化氮在 NMDA 介导的体内毒性中的双重作用。

• DOI: 10.1038/jcbfm.1995.115
• 发表时间: 1995
• 期刊: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.
• 作者: Globus,MY;Prado,R;Sanchez-Ramos,J;Zhao,W;Dietrich,WD;Busto,R;Ginsberg,MD
• 通讯作者: Ginsberg,MD

Ischemic injury in the brain. Role of oxygen radical-mediated processes.

大脑缺血性损伤。

• DOI: 10.1111/j.1749-6632.1989.tb22615.x
• 发表时间: 1989
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Watson,BD;Ginsberg,MD
• 通讯作者: Ginsberg,MD

MORPHOLOGICAL MANIFESTATIONS OF REPERFUSION INJURY IN BRAIN

• DOI: 10.1111/j.1749-6632.1994.tb36713.x
• 发表时间: 1994-01-01
• 期刊: CELLULAR, BIOCHEMICAL, AND MOLECULAR ASPECTS OF REPERFUSION INJURY
• 作者: DIETRICH, WD