Equivocal roles of tissue-type plasminogen activator in stroke-induced injury

• Published in: Trends in neurosciences (Regular ed.) Vol. 27; no. 3; pp. 155 - 160
• Main Authors: Benchenane, Karim, López-Atalaya, José P., Fernández-Monreal, Mónica, Touzani, Omar, Vivien, Denis
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2004; Elsevier Science; Elsevier Sequoia S.A
• Subjects: Animals; Biological and medical sciences; Cell Death - drug effects; Disease Models, Animal; Fibrinolytic Agents - adverse effects; Fibrinolytic Agents - therapeutic use; Glutamic Acid - metabolism; Humans; Medical sciences; Nervous system; Neuroglia - drug effects; Neurology; Neurons - drug effects; Neuroprotective Agents - adverse effects; Neuroprotective Agents - therapeutic use; Side effects; Signal Transduction - drug effects; Stroke; Stroke - complications; Stroke - drug therapy; Thrombolytic drugs; Thrombolytic Therapy - methods; Tissue Plasminogen Activator - adverse effects; Tissue Plasminogen Activator - therapeutic use; Transforming Growth Factor beta - therapeutic use; Transforming Growth Factor beta1; Vascular diseases and vascular malformations of the nervous system; Nervous system diseases; Stroke; Glial cell; Serine endopeptidases; Enzyme; Cardiovascular disease; Review; Thrombolytic agent; t-Plasminogen activator; Cerebral disorder; Vascular disease; Peptidases; Neuron; Treatment; Central nervous system disease; Hydrolases; Cerebrovascular disease
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2003.12.011

Stroke represents a major health problem in the ever-ageing population of industrialized nations. Each year, over three million people in the USA alone suffer from this affliction. Stroke, which results from the obstruction of an intra- or extra-cerebral artery, induces irreversible neuronal damage. The clot-busting drug tissue-type plasminogen activator (tPA) is the only FDA-approved therapy for acute stroke. Although tPA has been successfully used to treat myocardial infarction due to clot formation, its use in the treatment of occlusive cerebrovascular diseases remains controversial. Indeed, tPA is clearly beneficial as a thrombolytic agent. However, increasing evidence suggests that tPA could have direct and deleterious effects on neurons and glial cells.