Oxidative Stress Biomarkers of Brain Damage: Hyperacute Plasma F2-Isoprostane Predicts Infarct Growth in Stroke.

Ken Arai, Karen L Furie, Steven K Feske, Paul E Milbury, Jeffrey B Blumberg, Eng H Lo, Gordon J Harris, Ona Wu, Loc-Duyen D Pham, Angel T Som, Svetlana Lorenzano, Allison J Dipietro, Tijy K Thankachan, Rebecca E Green, Matthew B Maas, Fabricio O Lima, Hua Li, Muhib Khan, Natalia S Rost

Journal: Stroke 2018;49(3):630-637

PMID: 29371434

Abstract

BACKGROUND AND PURPOSE

Oxidative stress is an early response to cerebral ischemia and is likely to play an important role in the pathogenesis of cerebral ischemic injury. We sought to evaluate whether hyperacute plasma concentrations of biomarkers of oxidative stress, inflammation, and tissue damage predict infarct growth (IG).

METHODS

We prospectively measured plasma F2-isoprostane (F2-isoP), urinary 8-oxo-7,8-dihydro-2'-deoxyguoanosine, plasma oxygen radical absorbance capacity assay, high sensitivity C reactive protein, and matrix metalloproteinase 2 and 9 in consecutive patients with acute ischemic stroke presenting within 9 hours of symptom onset. Patients with baseline diffusion-weighted magnetic resonance imaging and follow-up diffusion-weighted imaging or computed tomographic scan were included to evaluate the final infarct volume. Baseline diffusion-weighted imaging volume and final infarct volume were analyzed using semiautomated volumetric method. IG volume was defined as the difference between final infarct volume and baseline diffusion-weighted imaging volume.

RESULTS

A total of 220 acute ischemic stroke subjects were included in the final analysis. One hundred seventy of these had IG. Baseline F2-isoP significantly correlated with IG volume (Spearman ρ=0.20; =0.005) and final infarct volume (Spearman ρ=0.19; =0.009). In a multivariate binary logistic regression model, baseline F2-isoP emerged as an independent predictor of the occurrence of IG (odds ratio, 2.57; 95% confidence interval, 1.37-4.83; =0.007). In a multivariate linear regression model, baseline F2-isoP was independently associated with IG volume (B, 0.38; 95% confidence interval, 0.04-0.72; =0.03).

CONCLUSIONS

Elevated hyperacute plasma F2-isoP concentrations independently predict the occurrence of IG and IG volume in patients with acute ischemic stroke. If validated in future studies, measuring plasma F2-isoP might be helpful in the acute setting to stratify patients with acute ischemic stroke for relative severity of ischemic injury and expected progression.

© 2018 American Heart Association, Inc.

Address: From the J. Philip Kistler Stroke Research Center, Department of Neurology (S.L., N.S.R., F.O.L., M.B.M., R.E.G., T.K.T., A.J.D.), Department of Radiology (H.L., G.J.H.), and Neuroprotection Research Laboratory, Neuroscience Center, Departments of Neurology and Radiology (K.A., A.T.S., L.-D.D.P., E.H.L.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Neurology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence (M.K., K.L.F.); Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (O.W.); Antioxidant Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (J.B.B.) and Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy (P.E.M.), Tufts University, Boston, MA; and Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.K.F.). [email protected].; From the J. Philip Kistler Stroke Research Center, Department of Neurology (S.L., N.S.R., F.O.L., M.B.M., R.E.G., T.K.T., A.J.D.), Department of Radiology (H.L., G.J.H.), and Neuroprotection Research Laboratory, Neuroscience Center, Departments of Neurology and Radiology (K.A., A.T.S., L.-D.D.P., E.H.L.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Neurology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence (M.K., K.L.F.); Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown (O.W.); Antioxidant Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging (J.B.B.) and Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy (P.E.M.), Tufts University, Boston, MA; and Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.K.F.).
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