Tissue-type plasminogen activator as a therapeutic target in stroke

Abstract

Background: Ischemic stroke is a leading cause of morbidity and mortality worldwide and recombinant human tissue-type plasminogen activator (tPA) is the prominent therapeutic among very few therapeutics used in its treatment. Due to complications attributed to the drug, most notably transformation of ischemia to hemorrhage, tPA is only used in a small number of ischemic stroke cases, albeit significantly more often in specialized stroke centers. Objective: What are the mechanisms of tPA action and side effects in ischemic stroke, and can the knowledge about these mechanisms aid in making tPA a more efficacious and safe therapeutic or in developing alternative therapeutics? Methods: tPA use and alternative/combination therapies in acute ischemic stroke treatment are summarized. The review focuses on literature concerning tPA neurotoxicity and its implications for further development of tPA as a stroke therapeutic. Results/conclusion: Exogenously administered recombinant tPA and endogenous tPA have both turned into promising therapeutic targets for the stroke patient.

Keywords::

• hemorrhagic conversion
• ischemia
• neuroserpin
• tissue plasminogen activator