Oxidative Stress After Thrombolysis-Induced Reperfusion in Human Stroke

Abstract

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...

Serum Pro-Oxidant-Antioxidant Balance, Advanced Oxidized Protein Products (AOPP) and Protein Carbonyl in Patients With Stroke

“…Studies in the field of oxidative stress and clinical implications revealed that generation of free radicals prompting oxidative stress plays a role in pathogenesis of the brain injuries (13). In normal condition, oxidants and antioxidants are in a balance status (14,15).…”

Fluidity and cytosolic Ca2+ concentration of circulating polymorphonuclear leukocytes at baseline in some chronic and acute clinical conditions: review of our survey

“…In subjects with juvenile AMI in whom we investigated plasma lipid peroxidation, expressed as TBARS, and plasma protein oxidation, expressed as carbonyl groups, a marked increase in both parameters was found at the initial stage of AMI [39,40]. The same behavior was present in AIS patients, in whom the increase in lipid peroxidation and protein oxidation, besides being evident at admission and 24 hours later [41], persisted for some months after the onset of AIS [42].…”

Serum myeloperoxidase chlorinating activity in acute ischemic stroke

“…Nađeno je (Grafik 1a) da je aktvinost MPO u serumu za oko 50% veća u grupi sa IMU u odnosu na kontrolnu grupu (67.2 U/L vs. 92.3 U/L, kod kontrole i kod pacijenata; p < 0.05). Iako za sada u literaturi ne postoje podaci o hlorinišućoj aktivnosti ekstracelularne MPO kod pacijenata sa IMU, Cojocaru i saradnici su našli za oko 30% veće koncentracije proteina MPO u serumu u akutnoj fazi IMU [11], dok je u jednoj drugoj studiji koncentracija MPO bila dvostruko veća od kontrolnih vrednosti [16].…”

“…Aleksandrova i saradnici su pokazali da iako je broj neutrofila bio proporcionalan težini IMU, sposobnost aktivacije, degranulacije i stvaranja oksidanasa nisu odgovarali kliničkoj težini bolesti [15]. U studiji Dominguez i saradnika nije bilo nikakve korelacije koncentracije MPO sa NIHSS skorom, kao pokazateljem kliničke težine bolesti [16]. Ni u našoj studiji nije postojala statistički značajna korelacija između NIHSS skora i MPO aktivnosti, kao ni između MPO aktivnosti i koncentracije hloramina (Tabela 3).…”