Abstract WP309: Association of Molecular Markers with Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage
Background and Purpose: Perihematomal edema (PHE) contributes to secondary brain injury in intracerebral hemorrhage (ICH). Increase of matrix metalloproteinases (MMPs) and growth factors (GFs) 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 PHE 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 in order to evaluate PHE. Concentrations of MMP-3, MMP-9, as well as vascular endothelial growth factor (VEGF) and Angiopoietin-1(Ang-1) on admission were determined by enzyme-linked immunosorbent assays. Clinical outcome was assessed by modified Rankin Scale (mRS) at 90days.
Results: Increased MMP-3 levels were independently associated with PHE volume (P<0.05). Cytotoxic edema (CE) surrounding the hematoma was seen in 36 (61%) cases on 3-day MRI. CE 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 VEGF and Ang-1 predicted poor clinical outcome at 90 days (mRS>3) independent of stroke severity and hematoma volume at baseline (OR 25.3, P=0.035; OR 68.9, P=0.023; respectively).
Conclusion: Metalloproteinases 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.
- © 2012 by American Heart Association, Inc.