Plasmin-dependent modulation of the blood-brain barrier: a major consideration during tPA-induced thrombolysis?

J Cereb Blood Flow Metab. 2014 Aug;34(8):1283-96. doi: 10.1038/jcbfm.2014.99. Epub 2014 Jun 4.

Abstract

Plasmin, the principal downstream product of tissue-type plasminogen activator (tPA), is known for its potent fibrin-degrading capacity but is also recognized for many non-fibrinolytic activities. Curiously, plasmin has not been conclusively linked to blood-brain barrier (BBB) disruption during recombinant tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the substantial involvement of tPA in the modulation of BBB permeability and the co-existence of tPA and plasminogen in both blood and brain throughout the ischemic event. Here, we review the work that argues a role for plasmin together with endogenous tPA or rtPA in BBB alteration, presenting the overall controversy around the topic yet creating a rational case for an involvement of plasmin in this process.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / metabolism
  • Fibrinolysin / metabolism*
  • Fibrinolysin / pharmacology
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / blood
  • Fibrinolytic Agents / metabolism
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Recombinant Proteins
  • Stroke / drug therapy*
  • Stroke / metabolism
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / blood
  • Tissue Plasminogen Activator / metabolism
  • Tissue Plasminogen Activator / therapeutic use*

Substances

  • Fibrinolytic Agents
  • Recombinant Proteins
  • Tissue Plasminogen Activator
  • Fibrinolysin