title: Injury-induced 92-kilodalton gelatinase and urokinase expression in rat brain.
abstract: BACKGROUND
  Proteolytic disruption of the extracellular matrix is important in pathologic processes. We have shown that activated 72-kilodalton (kd) type IV collagenase injected intracerebrally attacks brain extracellular matrix and opens the blood-brain barrier. Therefore, we tested the hypothesis that endogenous production of matrix-degrading proteases may be a factor in secondary brain injury.
  
  
  METHODS
  Adult rats had a hemorrhagic injury produced by injection of 0.4 units of bacterial collagenase into the caudate/putamen. Endogenous production of matrix metalloproteinases and plasminogen activators (PA) was measured by substrate-gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis (zymography) at 1, 4, 8, 16, 24, and 48 hours, and 7 and 14 days after the injury.
  
  
  RESULTS
  Gelatin-containing zymograms had bands of the expected molecular weights from the injected bacterial collagenase at 1 hour. By 8 hours a new 92-kd gelatinase was seen in zymograms. EDTA eliminated the 92-kd band, indicating that it was a metalloproteinase. The 92-kd type IV collagenase/gelatinase was maximally increased by 24 hours (p < 0.0001). Plasminogen-casein zymography showed 40- and 60-kd bands from PA. The 40-kd PA reached a maximum at 24 hours (p < 0.05) and remained elevated for 7 days. Amiloride completely eliminated the 40-kd band and reduced the 60-kd band, suggesting that they were a urokinase-type PA.
  
  
  CONCLUSIONS
  Hemorrhagic injury induces both 92-kd type IV collagenase/gelatinase and 40-kd urokinase-plasminogen activator expression in brain. We propose that metalloproteinases and serine proteases take part in a proteolytic cascade that breaks down extracellular matrix, opening the blood-brain barrier with secondary brain edema and cell death.
authors.affiliation: Department of Neurology, University of New Mexico School of Medicine, Albuquerque.
authors.forename: G A
authors.initials: GA
authors.lastname: Rosenberg
authors.forename: J E
authors.initials: JE
authors.lastname: Dencoff
authors.forename: P G
authors.initials: PG
authors.lastname: McGuire
authors.forename: L A
authors.initials: LA
authors.lastname: Liotta
authors.forename: W G
authors.initials: WG
authors.lastname: Stetler-Stevenson
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001930:Brain Injuries / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D018093:Gelatinases / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000584:Amiloride; D014568:Urokinase-Type Plasminogen Activator; D018093:Gelatinases