cyclosporine treatment reduces oxygen free radical generation and oxidative stress in the brain of hypoxia-reoxygenated newborn piglets环孢霉素治疗减少氧自由基生成和氧化应激的大脑hypoxia-reoxygenated新生的小猪.pdfVIP

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cyclosporine treatment reduces oxygen free radical generation and oxidative stress in the brain of hypoxia-reoxygenated newborn piglets环孢霉素治疗减少氧自由基生成和氧化应激的大脑hypoxia-reoxygenated新生的小猪.pdf

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cyclosporine treatment reduces oxygen free radical generation and oxidative stress in the brain of hypoxia-reoxygenated newborn piglets环孢霉素治疗减少氧自由基生成和氧化应激的大脑hypoxia-reoxygenated新生的小猪

Cyclosporine Treatment Reduces Oxygen Free Radical Generation and Oxidative Stress in the Brain of Hypoxia- Reoxygenated Newborn Piglets 1. 2. 2 3 3 1 Richdeep S. Gill , Tze-Fun Lee , Jiang-Qin Liu , Hetal Chaudhary , Dion R. Brocks , David L. Bigam , Po-Yin Cheung1,2* 1 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada, 2 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada, 3 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada Abstract Oxygen free radicals have been implicated in the pathogenesis of hypoxic-ischemic encephalopathy. It has previously been shown in traumatic brain injury animal models that treatment with cyclosporine reduces brain injury. However, the potential neuroprotective effect of cyclosporine in asphyxiated neonates has yet to be fully studied. Using an acute newborn swine model of hypoxia-reoxygenation, we evaluated the effects of cyclosporine on the brain, focusing on hydrogen peroxide (H O ) production and markers of oxidative stress. Piglets (1–4 d, 1.4–2.5 kg) were block-randomized 2 2 into three hypoxia-reoxygenation experimental groups (2 h hypoxia followed by 4 h reoxygenation)(n = 8/group). At 5 min after reoxygenation, piglets were given either i.v. saline (placebo, controls) or cyclosporine (2.5 or 10 mg/kg i.v. bolus) in a blinded-randomized fashion. An additional sham-operated group (n = 4) underwent no hypoxia-reoxygenation. Systemic hemodynamics, carotid arterial blood flow (transit-time ultrasonic probe), cerebral cortical H2O2 production (electrochem- ical sensor), cerebral tissue glutath