title: Association of molecular markers with perihematomal edema and clinical outcome in intracerebral hemorrhage.
abstract: OBJECTIVE
  Perihematomal edema contributes to secondary brain injury in intracerebral hemorrhage (ICH). Increase of matrix metalloproteinases (MMPs) and growth factors is considerably involved in blood-brain barrier disruption and neuronal cell death in ICH models. We therefore hypothesized that increased levels of these molecular markers are associated with perihematomal edema and clinical outcome in ICH patients.
  
  
  METHODS
  Fifty-nine patients with spontaneous ICH admitted within 24 hours of symptom onset were prospectively investigated. Noncontrast CT was performed on admission for diagnosis of ICH and quantification of initial hematoma volume. MRI was performed on day 3 to evaluate perihematomal edema. Concentrations of MMP-3, MMP-9, as well as vascular endothelial growth factor and angiopoietin-1 on admission were determined by enzyme-linked immunosorbent assays. Clinical outcome was assessed by modified Rankin Scale at 90 days.
  
  
  RESULTS
  Increased MMP-3 levels were independently associated with perihematomal edema volume (P<0.05). Cytotoxic edema surrounding the hematoma was seen in 36 (61%) cases on 3-day MRI. Cytotoxic edema did not correlate with the level of any of the biomarkers studied. Levels of MMP-3 ≥12.4 ng/mL and MMP-9 ≥192.4 ng/mL but not vascular endothelial growth factor and angiopoietin-1 predicted poor clinical outcome at 90 days (modified Rankin Scale >3) independent of stroke severity and hematoma volume at baseline (odds ratio, 25.3, P=0.035; odds ratio, 68.9, P=0.023; respectively).
  
  
  CONCLUSIONS
  MMPs 3 and 9 seem to be significantly involved in secondary brain injury and outcome after primary ICH in humans, and thus should be further evaluated as targets for therapeutic strategies in this devastating disorder.
authors: Department of Neurology, Capital Medical University, Beijing, China.
authors: Na
authors: N
authors: Li
authors: Yan Fang
authors: YF
authors: Liu
authors: Li
authors: L
authors: Ma
authors: Hans
authors: H
authors: Worthmann
authors: Yi Long
authors: YL
authors: Wang
authors: Yong Jun
authors: YJ
authors: Wang
authors: Yi Pei
authors: YP
authors: Gao
authors: Peter
authors: P
authors: Raab
authors: Reinhard
authors: R
authors: Dengler
authors: Karin
authors: K
authors: Weissenborn
authors: Xing Quan
authors: XQ
authors: Zhao
mesh_terms: D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001929:Brain Edema / Q000097:blood / Q000209:etiology* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D005260:Female; D005500:Follow-Up Studies; D006406:Hematoma / Q000150:complications* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042683:Angiopoietin-1; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9