Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke

被引:249
作者
Wang, XY
Tsuji, K
Lee, SR
Ning, MM
Furie, KL
Buchan, AM
Lo, EH
机构
[1] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA
[3] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada
[4] Univ Calgary, Stroke Program, Calgary Brain Inst, Calgary, AB T2N 1N4, Canada
关键词
blood-brain barrier; cerebral ischemia; hemorrhage; neuroprotection;
D O I
10.1161/01.STR.0000143219.16695.af
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Reperfusion therapy with tissue plasminogen activator (tPA) is a rational therapy for acute ischemic stroke. Properly titrated use of tPA improves clinical outcomes. However, there is also an associated risk of hemorrhagic transformation after tPA therapy. Emerging data now suggest that some of these potentially neurotoxic side effects of tPA may be due to its signaling actions in the neurovascular unit. Besides its intended role in clot lysis, tPA is also an extracellular protease and signaling molecule in brain. tPA mediates matrix remodeling during brain development and plasticity. By interacting with the NMDA-type glutamate receptor, tPA may amplify potentially excitotoxic calcium currents. At selected concentrations, tPA may be vasoactive. Finally, by augmenting matrix metalloproteinase (NIMP) dysregulation after stroke, tPA may degrade extracellular matrix integrity and increase risks of neurovascular cell death, blood-brain barrier leakage, edema, and hemorrhage. Understanding these pleiotropic actions of tPA may reveal new therapeutic opportunities for combination stroke therapy.
引用
收藏
页码:2726 / 2730
页数:5
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