Neutralizing the neurotoxic effects of exogenous and endogenous tPA

被引：62

作者：

Armstead, William M.

Nassar, Taher

Akkawi, Saed

Smith, Douglas H.

Chen, Xiao-Han

Cines, Douglas B.

Higazi, Abd Al-Roof ^{[1
]}

机构：

[1] Hadassah Univ Hosp, Dept Clin Biochem, IL-91120 Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91120 Jerusalem, Israel

[3] Univ Penn, Dept Anesthesia & Crit Care, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA

[6] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

来源：

NATURE NEUROSCIENCE | 2006年 / 9卷 / 09期

关键词：

D O I：

10.1038/nn1757

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The clinical use of tissue-type plasminogen activator (tPA) in the treatment of stroke is profoundly constrained by its serious side effects. We report that the deleterious effects of tPA on cerebral edema and intracranial bleeding are separable from its fibrinolytic activity and can be neutralized. A hexapeptide (EEIIMD) corresponding to amino acids 350-355 of plasminogen activator inhibitor type 1 (PAI-1) abolished the tPA-induced increase in infarct size and intracranial bleeding in both mechanical and embolic models of stroke in rats, and reduced brain edema and neuronal loss after traumatic brain injury in pigs. These experiments suggest mechanisms to reduce the neurotoxic effects of tPA without compromising its fibrinolytic activity, through the use of selective antagonists and new tPA formulations.

引用

页码：1150 / 1155

页数：6

共 32 条

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