This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hermann, D. M. Articles by Matter, C. M. Search for Related Content PubMed PubMed Citation Articles by Hermann, D. M. Articles by Matter, C. M. Related Collections Acute Cerebral Infarction Thrombolysis Related Article

(Circulation. 2007;116:363-365.)
© 2007 American Heart Association, Inc.

Editorial

Tissue Plasminogen Activator–Induced Reperfusion Injury After Stroke Revisited

Dirk M. Hermann, MD; Christian M. Matter, MD

From the Departments of Neurology (D.M.H.) and Cardiology, Cardiovascular Center (C.M.M.), University Hospital Zurich; and Cardiovascular Research (C.M.M.), Institute of Physiology, University of Zurich, Zurich, Switzerland.

Reprint requests to Dr Dirk M. Hermann, Department of Neurology, University Hospital Zurich, Frauenklinikstr 26, CH-8091 Zürich, Switzerland. E-mail dirk.hermann@usz.ch

Key Words: Editorials • blood-brain barrier • inflammation • mast cells • tissue plasminogen activator

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Intravenous thrombolysis with tissue plasminogen activator (tPA) is an established treatment of acute ischemic stroke in humans.¹ When delivered within 3 hours after symptom onset, tPA reduces neurological deficits and improves the functional outcome of stroke patients.¹ However, this improvement in recovery is achieved at the expense of an increased incidence in symptomatic intracranial hemorrhage, which occurs in 6% of patients.¹ Intracranial hemorrhage is a typical complication of thrombolysis in acute ischemic stroke. Hemorrhages markedly reduce the therapeutic benefit of tPA.

Article p 411

Parenchymal bleeding after stroke is attributed to leakiness of the blood-brain barrier.² On acute ischemia, fine-tuned chemokine responses lead to the recruitment of T cells, macrophages, and mast cells (MCs) into the brain tissue.³ These inflammatory cells release a variety of proteolytic enzymes, including matrix metalloproteinase (MMP)-2 and MMP-9,³ that induce blood-brain barrier breakdown and facilitate vascular rupture. On release of other chemoattractant molecules, polymorphonuclear neutrophils enter the brain parenchyma, imposing massive oxidative stress on the reperfused tissue.³

tPA therapy of acute ischemic stroke increases both reperfusion damage and hemorrhage risk. As such, the thrombolytic promotes matrix degradation in the ischemic brain parenchyma via activation of MMP-9.⁴ Furthermore, it imposes oxidative stress by upregulation of inducible nitric oxide synthase, which is also a proinflammatory enzyme,⁵ and induces vascular disturbances reflected by downregulation of endothelial nitric oxide synthase.^6,7 As a consequence, neuronal injury is facilitated in a caspase-8–dependent way.⁸ This process is controlled by activated protein C.^4,8 The fact that the half-life of tPA itself is short . . . [Full Text of this Article]

Related Article:

Issue Highlights
Circulation 2007 116: 359. [Extract] [Full Text]