title: tPA in the injured central nervous system: different scenarios starring the same actor?
abstract: When in 1947, Astrup and Permin reported that animal tissues contain fibrinokinase, a plasminogen activator, and when Pennica and colleagues (Pennica et al., 1983) cloned and expressed human tissue plasminogen activator (tPA) in Escherichia coli in 1983, they might did not realize how much their pioneer work would impact the life of millions of patients suffering from myocardial infarction or ischemic stroke. Some years after, accumulating evidence shows that tPA is not just a plasminogen activator of endothelial origin. Indeed, the main function of tPA released from the endothelium is to convert fibrin-bound plasminogen into active plasmin, thus dissolving the fibrin meshwork of blood clots. But this serine protease is also expressed by several cell types, and its beneficial and deleterious actions stand beyond fibrinolysis or even proteolysis. We will review here the reported effects and mechanisms of action of tPA in the course of three different pathologies of the central nervous system (CNS): spinal cord injury, ischemic stroke and multiple sclerosis. While these three disorders have distinct aetiologies, they share some pathogenic mechanisms. We will depict the main "good" and "bad" sides of tPA described to date during each of these pathological situations, as well as the proposed mechanisms explaining these effects. We speculate that due to common pathogenic pathways, tPA's actions described in one particular disease could in fact occur in the others. Finally, we will evaluate if tPA could be a therapeutic target for these pathologies. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors.affiliation: INSERM U919, "Serine Proteases and Pathophysiology of the Neurovascular Unit", UMR CNRS 6232 Cinaps, GIP Cyceron, University of Caen, Bd H. Becquerel, BP 5229, 14074 Caen Cedex, France.
authors.forename: Sighild
authors.initials: S
authors.lastname: Lemarchant
authors.forename: Fabian
authors.initials: F
authors.lastname: Docagne
authors.forename: Evelyne
authors.initials: E
authors.lastname: Emery
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.forename: Carine
authors.initials: C
authors.lastname: Ali
authors.forename: Marina
authors.initials: M
authors.lastname: Rubio
mesh_terms: D002545:Brain Ischemia / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D006801:Humans; D009103:Multiple Sclerosis / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D010959:Tissue Plasminogen Activator