Oxidative stress after thrombolysis-induced reperfusion in human stroke.
OBJECTIVE
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 (P<0.01 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.
Domínguez
Carmen
C
Biochemistry and Molecular Biology Research Center, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Delgado
Pilar
P
Vilches
Angel
A
Martín-Gallán
Pilar
P
Ribó
Marc
M
Santamarina
Estevo
E
Molina
Carlos
C
Corbeto
Natalia
N
Rodríguez-Sureda
Victor
V
Rosell
Anna
A
Alvarez-Sabín
Jose
J
Montaner
Joan
J
D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015424:Reperfusion; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D015415:Biomarkers; D005343:Fibrinolytic Agents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D009195:Peroxidase; D010959:Tissue Plasminogen Activator