Elevated Peripheral Neutrophils and Matrix Metalloproteinase 9 as Biomarkers of Functional Outcome Following Subarachnoid HemorrhageReport as inadecuate




Elevated Peripheral Neutrophils and Matrix Metalloproteinase 9 as Biomarkers of Functional Outcome Following Subarachnoid Hemorrhage - Download this document for free, or read online. Document in PDF available to download.

Translational Stroke Research

, Volume 2, Issue 4, pp 600–607

First Online: 10 November 2011Received: 09 September 2011Revised: 10 October 2011Accepted: 12 October 2011

Abstract

There is growing evidence supporting the role of inflammation in early brain injury and cerebral vasospasm following subarachnoid hemorrhage SAH. Matrix metalloproteinases MMPs are released by inflammatory cells and can mediate early brain injury via disruption of the extracellular matrix and mediate vasospasm by cleaving endothelin-1 into vasoactive fragments. We hypothesize that inflammation marked by neutrophil elevation and MMP-9 release in human SAH is associated with vasospasm and with poor clinical outcome. We enrolled consecutive SAH subjects N = 55, banked serial blood and cerebrospinal fluid CSF samples, and evaluated their 3-month modified Rankin scores mRS. Vasospasm was defined as >50% vessel caliber reduction on angiography 6–8 days post-SAH. A poor outcome was defined as mRS > 2. We compared blood leukocyte and neutrophil counts during post-SAH days 0–14 with respect to vasospasm and 3-month outcome. In a subset of SAH subjects N = 35, we compared blood and CSF MMP-9 by enzyme-linked immunosorbent assay ELISA on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to 3-month outcome. Persistent elevation of blood leukocyte p = 0.0003 and neutrophil p = 0.0002 counts during post-SAH days 0–14 are independently associated with vasospasm after adjustment for major confounders. In the same time period, blood neutrophil count post-SAH days 2–3, p = 0.018, blood MMP-9 post-SAH days 4–5, p = 0.045, and CSF MMP-9 post-SAH days 2–3, p = 0.05 are associated with poor 3-month SAH clinical outcome. Neutrophil count correlates with blood MMP-9 post-SAH days 6–8, R = 0.39; p = 0.055; post-SAH days 10–14, R = 0.79; p < 0.0001, and blood MMP-9 correlates with CSF MMP-9 post-SAH days 4–5, R = 0.72; p = 0.0002. Elevation of CSF MMP-9 during post-SAH days 0–14 is associated with poor 3-month outcome p = 0.0078. Neither CSF nor blood MMP-9 correlates with vasospasm. Early rise in blood neutrophil count and blood and CSF MMP-9 are associated with poor 3-month SAH clinical outcome. In blood, neutrophil count correlates with MMP-9 levels, suggesting that neutrophils may be an important source of blood MMP-9 early in SAH. Similarly, CSF and blood MMP-9 correlate positively early in the course of SAH, suggesting that blood may be an important source of CSF MMP-9. Blood and CSF MMP-9 are associated with clinical outcome but not with vasospasm, suggesting that MMP-9 may mediate brain injury independent of vasospasm in SAH. Future in vitro studies are needed to investigate the role of MMP-9 in SAH-related brain injury. Larger clinical studies are needed to validate blood and CSF MMP-9 as potential biomarkers for SAH outcome.

KeywordsSubarachnoid hemorrhage Biomarker Matrix metalloproteinase Inflammation Neutrophils Vasospasm Outcome Eng H. Lo and MingMing Ning contributed equally to this manuscript.

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Author: S. H.-Y. Chou - S. K. Feske - S. L. Simmons - R. G. J. Konigsberg - S. C. Orzell - A. Marckmann - G. Bourget - D. J.

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