期刊
STROKE
卷 39, 期 1, 页码 100-104出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.107.488189
关键词
cerebrovascular disorders; metalloproteinase; oxidative stress
资金
- AGENCY FOR HEALTHCARE RESEARCH AND QUALITY [R01HS011392] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [P01CA077839] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR001066] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK048831] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P01ES013125] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P50GM015431, P01GM015431] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [K23NS051588, R01NS038731, R21NS052498, K23NS042720, R01NS037074, R01NS040529] Funding Source: NIH RePORTER
- AHRQ HHS [R01-HS011392] Funding Source: Medline
- NCI NIH HHS [CA77839] Funding Source: Medline
- NCRR NIH HHS [M01-RR-01066] Funding Source: Medline
- NIDDK NIH HHS [DK48831] Funding Source: Medline
- NIEHS NIH HHS [ES13125] Funding Source: Medline
- NIGMS NIH HHS [GM15431] Funding Source: Medline
- NINDS NIH HHS [K23-NS051588, K23 NS42720, R01-NS40529, R21NS052498, R01-NS38731, R01-NS37074] Funding Source: Medline
Background and Purpose-Experimental stroke studies indicate that oxidative stress is a major contributing factor to ischemic cerebral injury. Oxidative stress is also implicated in activation of matrix metalloproteinases (MMPs) and blood-brain barrier injury after ischemia-reperfusion. Plasma biomarkers of oxidative stress may have utility as early indicators of efficacy in Phase 2 trials of antioxidant therapies in human stroke. To date, a valid biomarker has been unavailable. We measured F2-isoprostanes (F2IPs), free-radical induced products of neuronal arachadonic acid peroxidation, in acute ischemic stroke. We aimed to determine the change in plasma F2IP levels over time and relationship with plasma MMP-9 in tPA-treated and tPA-untreated stroke patients. Methods-We performed a case-control study of consecutive ischemic stroke patients (25 tPA-treated and 27 tPA-untreated) presenting within 8 hours of stroke onset. Controls were individuals without prior stroke from a primary care clinic network serving the source population from which cases were derived. Infarct volume was determined on acute diffusion-weighted MRI (DWI) performed within 48 hours using a semi-automated computerized segmentation algorithm. Phlebotomy was performed at < 8 hours, 24 hours, 2 to 5 days, and 4 to 6 weeks. F2IPs were measured by gas chromatography/mass spectrometry and MMP-9 by ELISA. Prestroke antioxidant dietary intake was measured by the 24-hour recall method. Results-In 52 cases and 27 controls, early (median 6 hours postonset) F2IPs were elevated in stroke cases compared with controls (medians 0. 041 versus 0.0295pg/mL, P = 0.012). No difference in F2IPSs was present at later time points. Early plasma F2IPs correlated with MMP-9 in all patients (P = 0.01) and the tPA-treated subgroup (P = 0.02). No correlation was found with NIHSS, DWI infarct volume, 90-day Rankin score, or C-reactive protein (P > 0.05 for all). Conclusions-In early human stroke we found evidence of increased oxidative stress and a relationship with MMP-9 expression, supporting findings from experimental studies.
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