title: 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.
  
  
  CONCLUSIONS
  Exogenously administered recombinant tPA and endogenous tPA have both turned into promising therapeutic targets for the stroke patient.
authors.affiliation: Stony Brook University, Department of Pharmacological Sciences, Stony Brook, NY 11794-8651, USA.
authors.forename: Iordanis
authors.initials: I
authors.lastname: Gravanis
authors.forename: Stella E
authors.initials: SE
authors.lastname: Tsirka
mesh_terms: D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator