title: Plasmin-dependent modulation of the blood-brain barrier: a major consideration during tPA-induced thrombolysis?
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.
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: Be'eri
authors.initials: B
authors.lastname: Niego
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Medcalf
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism* / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D011994:Recombinant Proteins; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin