title: Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke.
abstract: OBJECTIVE
  Abnormal expression of some matrix metalloproteinases (MMP) has shown to play a deleterious role in brain injury in experimental models of cerebral ischemia. We aimed to investigate MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in brain parenchyma in both ischemic and hemorrhagic strokes.
  
  
  METHODS
  Postmortem fresh brain tissue from 6 ischemic and 8 hemorrhagic stroke patients was obtained within the first 6 hours after death. Finally, 78 brain tissue samples from different areas (infarct, peri-infarct, perihematoma and contralateral hemisphere) were studied. To quantify gelatinase content we performed gelatin zymograms that were confirmed by Western Blot Analysis, immunohistochemistry to localize MMP source, and in situ zymography to detect gelatinase activity.
  
  
  RESULTS
  Among ischemic cases, gelatin zymography showed increased MMP-9 content in infarct core although peri-infarct tissue presented also higher levels than contralateral hemisphere (P<0.0001 and P=0.042, respectively). Within infarct core, MMP-9 was mainly located around blood vessels, associated to neutrophil infiltration and activated microglial cells. In peri-infarct areas the major source of MMP-9 were microglial cells. Tissue around intracranial hemorrhage also displayed higher MMP-9 levels than contralateral hemisphere (P=0.008) in close relationship with glial cells. MMP-2 was constitutively expressed and remained invariable in different brain areas.
  
  
  CONCLUSIONS
  Our results demonstrate in situ higher levels of MMP-9 in human brain tissue after ischemic and hemorrhagic stroke, suggesting a contribution of MMP-9 to ischemic brain injury and perihematoma edema.
authors.affiliation: Department of Neurology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Rosell
authors.forename: Arantxa
authors.initials: A
authors.lastname: Ortega-Aznar
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
authors.forename: Israel
authors.initials: I
authors.lastname: Fernández-Cadenas
authors.forename: Marc
authors.initials: M
authors.lastname: Ribó
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications*; D002543:Cerebral Hemorrhage / Q000150:complications*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D020521:Stroke / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9