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

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

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Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.


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.

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