title: Plasmin deficiency leads to fibrin accumulation and a compromised inflammatory response in the mouse brain.
abstract: BACKGROUND
  Excess fibrin in blood vessels is cleared by plasmin, the key proteolytic enzyme in fibrinolysis. Neurological disorders and head trauma can result in the disruption of the neurovasculature and the entry of fibrin and other blood components into the brain, which may contribute to further neurological dysfunction.
  
  
  OBJECTIVE
  While chronic fibrin deposition is often implicated in neurological disorders, the pathological contributions attributable specifically to fibrin have been difficult to ascertain. An animal model that spontaneously acquires fibrin deposits could allow researchers to better understand the impact of fibrin in neurological disorders.
  
  
  METHODS
  Brains of plasminogen (plg)- and tissue plasminogen activator (tPA)-deficient mice were examined and characterized with regard to fibrin accumulation, vascular and neuronal health, and inflammation. Furthermore, the inflammatory response following intrahippocampal lipopolysaccharide (LPS) injection was compared between plg(-/-) and wild type (WT) mice.
  
  
  CONCLUSIONS
  Both plg(-/-) and tPA(-/-) mice exhibited brain parenchymal fibrin deposits that appear to result from reduced neurovascular integrity. Markers of neuronal health and inflammation were not significantly affected by proximity to the vascular lesions. A compromised neuroinflammatory response was also observed in plg(-/-) compared to WT mice following intrahippocampal LPS injection. These results demonstrate that fibrin does not affect neuronal health in the absence of inflammation and suggest that plasmin may be necessary for a normal neuroinflammatory response in the mouse CNS.
authors.affiliation: The Rockefeller University, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hultman
authors.forename: M
authors.initials: M
authors.lastname: Cortes-Canteli
authors.forename: A
authors.initials: A
authors.lastname: Bounoutas
authors.forename: A T
authors.initials: AT
authors.lastname: Richards
authors.forename: S
authors.initials: S
authors.lastname: Strickland
authors.forename: E H
authors.initials: EH
authors.lastname: Norris
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005342:Fibrinolysis; D006624:Hippocampus / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010958:Plasminogen / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin
keywords: fibrin; inflammation; plasmin; tissue plasminogen activator; vasculature