Background and Purpose-Animal models of transient ischemia suggest that oxygen-derived free radicals produced on reperfusion of ischemic brain could constitute the main cause of reperfusion injury. We aimed to determine the presence and role of lipid peroxidation and protein oxidation-related molecules after tissue plasminogen activator-induced recanalization in human stroke. Methods-A total of 160 patients with strokes involving the middle cerebral artery and treated with tissue plasminogen activator and 60 healthy controls were included. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale scores were obtained at baseline (pretreatment), 1 hour and 2 hours after tissue plasminogen activator bolus, and 12 hours and 24 hours after stroke onset. The main lipid peroxidation end-product malondialdehyde, advanced oxidation protein products, and plasma concentrations of myeloperoxidase were assessed. Results-At baseline, all oxidative stress biomarkers were higher than in control subjects (PϽ0.01 for all comparisons).Malondialdehyde remained high compared with controls during the study period, whereas myeloperoxidase concentrations were significantly raised at baseline, 1 hour after tissue plasminogen activator administration, and 12 hours after stroke onset. Malondialdehyde concentrations correlated with stroke severity and were associated with outcome and with hemorrhagic complications. Regarding recanalization, among those patients with middle cerebral artery recanalization by the end of tissue plasminogen activator infusion (44%) or anytime thereafter, no peaking of any of the studied molecules could be identified. Conclusions-Our study showed that systemic oxidative damage to lipids and proteins had already occurred at baseline in stroke. In contrast to animal studies, a relationship between free radical-mediated oxidative damage to lipids or proteins and reperfusion injury after arterial recanalization could not be established. (Stroke. 2010;41:653-660.)Key Words: stroke Ⅲ thrombolysis Ⅲ oxidative stress Ⅲ MDA Ⅲ AOPPs Ⅲ MPO O xidative stress, resulting from an imbalance in redox state in which pro-oxidants overwhelm antioxidant capacity, has emerged as a potential mechanism implicated in the pathogenesis and disease progression of many unrelated pathological processes, including cardiovascular diseases, cancer, and diabetes, and may therefore contribute significantly to disease mechanisms; 1 however, increased oxidative stress may also result from pathological processes. 2 Reactive oxygen species (ROS) are continuously generated in the body as a consequence of aerobic metabolism or as part of the body's defense against microorganisms. ROS are highly reactive to any or all molecular targets: lipids, proteins, nucleic acids, or carbohydrates, 1 modifying their chemical structure and generating oxidation-derived products, markers of biomolecular oxidative damage. 3 Increased ROS production has been demonstrated in ischemic stroke, both during ischemia and reperfusion, o...
