title: Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion.
abstract: OBJECTIVE
  During focal cerebral ischemia, the microvascular matrix (ECM), which participates in microvascular integrity, is degraded and lost when neurons are injured. Loss of microvascular basal lamina antigens coincides with rapid expression of select matrix metalloproteinases (MMPs). Plasminogen activators (PAs) may also play a role in ECM degradation by the generation of plasmin or by MMP activation.
  
  
  METHODS
  The endogenous expressions of tissue-type plasminogen activator (tPA), urokinase (uPA), and PA inhibitor-1 (PAI-1) were quantified in 10-microm frozen sections from ischemic and matched nonischemic basal ganglia and in the plasma of 34 male healthy nonhuman primates before and after middle cerebral artery occlusion (MCA:O).
  
  
  RESULTS
  Within the ischemic basal ganglia, tissue uPA activity and antigen increased significantly within 1 hour after MCA:O (2P<0.005). tPA activity transiently decreased 2 hours after MCA:O (2P=0.01) in concert with an increase in PAI-1 antigen (2P=0.001) but otherwise did not change. The transient decrease in free tPA antigen was marked by an increase in the tPA-PAI-1 complex (2P<0.001). No significant relations to neuronal injury or intracerebral hemorrhage were discerned.
  
  
  CONCLUSIONS
  The rapid increase in endogenous PA activity is mainly due to significant increases in uPA, but not tPA, within the ischemic basal ganglia after MCA:O. This increase and an increase in PAI-1 coincided with latent MMP-2 generation and microvascular ECM degeneration but not neuronal injury.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: N
authors.initials: N
authors.lastname: Hosomi
authors.forename: J
authors.initials: J
authors.lastname: Lucero
authors.forename: J H
authors.initials: JH
authors.lastname: Heo
authors.forename: J A
authors.initials: JA
authors.lastname: Koziol
authors.forename: B R
authors.initials: BR
authors.lastname: Copeland
authors.forename: G J
authors.initials: GJ
authors.lastname: del Zoppo
mesh_terms: D000208:Acute Disease; D000818:Animals; D001479:Basal Ganglia / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005780:Gelatin / Q000378:metabolism; D015151:Immunoblotting; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010215:Papio; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000097:blood; D010960:Plasminogen Activators / Q000096:biosynthesis* / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000097:blood
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D005780:Gelatin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator