title: A matrix metalloproteinase protein array reveals a strong relation between MMP-9 and MMP-13 with diffusion-weighted image lesion increase in human stroke.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) are involved in tissue destruction produced by the neuroinflammatory response that follows ischemic stroke. In the present study we use an MMP array to investigate the blood levels of several MMPs in stroke patients and its relation with brain tissue damage and neurological outcome.
  
  
  METHODS
  Twenty-four patients with middle cerebral artery occlusion who received thrombolytic therapy were included. Blood samples were drawn before tissue plasminogen activator treatment and an MMP array (multiplex enzyme-linked immunosorbent assay [ELISA]) was performed including gelatinases (MMP-2 and MMP-9), collagenases (MMP-1, MMP-8, and MMP-13), stromelysines (MMP-3 and MMP-10), and MMP endogen inhibitors (TIMP-1 and TIMP-2). To assess tissue lesion a serial multimodal MRI study was performed (pretreatment and at 24 hours).
  
  
  RESULTS
  Neither initial diffusion lesion nor hypoperfused volume was associated with metalloproteinase expression within the first 3 hours after stroke onset. Nevertheless, a strong correlation was found between MMP-9 and MMP-13 with diffusion-weighted image (DWI) lesion expansion (r=0.54, P=0.05 and r=0.60, P=0.017, respectively). Baseline levels of both MMP-9 (OR, 14;95% CI, 1.5 to 131; P=0.019) and MMP-13 (OR, 73; 95% CI, 3.9 to 1388; P=0.004) were independent predictors of final increase in brain infarct volume at 24 hours.
  
  
  CONCLUSIONS
  Our results demonstrate that within the neuroinflammatory response, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth despite thrombolytic therapy, suggesting its ultra-early role in brain injury.
authors.affiliation: Neurology Department, Universitat Autònoma de Barcelona, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Rosell
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arenillas
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Israel
authors.initials: I
authors.lastname: Fernández-Cadenas
authors.forename: Anna
authors.initials: A
authors.lastname: Penalba
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000368:Aged; D001921:Brain / Q000473:pathology*; D016923:Cell Death; D017364:Collagenases / Q000096:biosynthesis*; D004058:Diffusion; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D053506:Matrix Metalloproteinase 10; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D020784:Matrix Metalloproteinase 8 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008875:Middle Aged; D016017:Odds Ratio; D020521:Stroke / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology*; D015912:Thrombolytic Therapy; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D010959:Tissue Plasminogen Activator; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1