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(Stroke. 2004;35:1316.)
© 2004 American Heart Association, Inc.

Original Contributions

Temporal Profile of Matrix Metalloproteinases and Their Inhibitors After Spontaneous Intracerebral Hemorrhage

Relationship to Clinical and Radiological Outcome

José Alvarez-Sabín, MD, PhD; Pilar Delgado, MD; Sònia Abilleira, MD, PhD; Carlos A. Molina, MD, PhD; Juan Arenillas, MD; Marc Ribó, MD; Esteban Santamarina, MD; Manolo Quintana; Jasone Monasterio, MD, PhD Joan Montaner, MD, PhD

From Neurovascular Research Laboratory and the Stroke Unit (J.A.-S., P.D., S.A., C.A.M., J.A., M.R., E.S., M.Q., J. Montaner) and Vascular Biology and Hemostasis Laboratory (J. Monasterio), Hospital Universitario Vall d’Hebron, Barcelona, Spain.

Correspondence to Dr José Álvarez-Sabín, Unitat Neurovascular (Servei de Neurologia) 9 Planta, Hospital Universitario Vall d’Hebron, Passeig Vall d’Hebrón 119-129, 08035 Barcelona, Spain. E-mail josalvar{at}vhebron.net

Background and Purpose— Matrix metalloproteinases (MMPs) are related to blood–brain barrier disruption, and some members of this family have been recently involved in brain bleedings. We aimed to investigate the temporal profile of MMPs and their natural inhibitors (TIMPs) after acute intracerebral hemorrhage (ICH) and to study its influence on neuroimaging and clinical outcome.

Methods— MMP-2, MMP-9, and MMP-3, as well as TIMP-1 and TIMP-2, were serially determined by enzyme-linked immunosorbent assay on admission (<12 hours), and at 24 hours, 48 hours, 7 days, and 3 months in 21 ICH patients. ICH and perihematomal edema (PE) volumes were serially measured on baseline and follow-up computed tomography (48 hours, 7 days, and 3 months), just at the time of neurological assessment.

Results— Deep ICH was found in 62% patients. Baseline ICH volume did not influence MMP-TIMP level. Highest levels of MMP-2 and TIMP-2 were found at baseline, for MMP-9 and TIMP-1 at 24 hours, and for MMP-3 at 24 to 48 hours. Baseline MMP-9 was positively correlated to PE volume (r=0.67, P=0.004) and, conversely, its inhibitor TIMP-1 was negatively correlated to PE (r=–0.51, P=0.04). Mortality reached 35% and MMP-3 was the only MMP/TIMP related to mortality (7.5 versus 2.4 ng/mL; P=0.035) and its most powerful baseline predictor (odds ratio = 22, confidence interval: 1.5 to 314.2). Both MMP-9 and MMP-3 correlated to the residual scar volume at 3 months (r=0.68, P=0.01 for baseline MMP-9, and r=0.86, P<0.001 for 24-hour MMP-3).

Conclusions— A characteristic temporal profile of MMP/TIMP release exists in ICH. Increased MMP-9 is associated with PE, and increased MMP-3 is associated with mortality. Both molecules are related to residual cavity volume.

Key Words: brain edema • intracerebral hemorrhage • metalloproteinases • stroke

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