Tissue-type plasminogen activator in the ischemic brain: more than a thrombolytic

Trends Neurosci. 2009 Jan;32(1):48-55. doi: 10.1016/j.tins.2008.09.006. Epub 2008 Oct 27.


Thrombolysis with tissue-type plasminogen activator (tPA) is used for the treatment of patients with acute ischemic stroke. However, a growing body of evidence indicates that, besides the unquestionable benefit from its thrombolytic activity, tPA also has a deleterious effect on the ischemic brain including cytotoxicity and increased permeability of the neurovascular unit with the development of cerebral edema. Because an increasing number of acute stroke patients are treated with tPA, it is important to know the mechanisms of harmful effects of tPA on the ischemic brain. Here, the best studied pathways of tPA neurotoxicity are discussed along with future directions for a safer use of tPA as a thrombolytic agent in the setting of acute ischemic stroke.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Tissue Plasminogen Activator / pharmacology
  • Tissue Plasminogen Activator / therapeutic use*


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator