BACKGROUND: To investigate the protective effects of propofol in brain ischemia/reperfusion injury and the role of heme oxygenase-1 (HO-1) in this process. METHODS: Sprague-Dawley rats were randomly divided into 9 groups: sham-operated group; middle cerebral artery occlusion (MCAO) group; propofol 10, 20, and 50 mg/kg/h group (propofol 10, 20, 50 mg/kg/h infused at the onset of reperfusion for 30 min), ZnPPIX (a HO-1 activity inhibitor) group (ZnPPIX 20 μmol/kg administered 24 h before MCAO), and the other 3 groups received ZnPPIX followed by 10, 20, and 50 mg/kg/h propofol respectively. At 24 hours of reperfusion, neurological examinations were performed, and after neurological test, brain infarct size and volume, neuronal apoptosis, the level of HO-1 protein expression and HO-1 activity were observed in each group. RESULTS: Propofol significantly improved neurological deficits, reduced infarct volume, and attenuated neuron apoptosis compared with MCAO group alone. Increased HO-1 protein expression was observed in the ischemic penumbra and core of propofol group after transient MCAO. The selective HO-1 activity inhibitor, ZnPPIX, partially eliminated the neuroprotective effects of propofol. CONCLUSIONS: The neuroprotective effects of propofol postconditioning in brain ischemia/reperfusion injury may be partially through the induction of the HO-1 expression.
BACKGROUND: To investigate the protective effects of propofol in brain ischemia/reperfusion injury and the role of heme oxygenase-1 (HO-1) in this process. METHODS:Sprague-Dawley rats were randomly divided into 9 groups: sham-operated group; middle cerebral artery occlusion (MCAO) group; propofol 10, 20, and 50 mg/kg/h group (propofol 10, 20, 50 mg/kg/h infused at the onset of reperfusion for 30 min), ZnPPIX (a HO-1 activity inhibitor) group (ZnPPIX 20 μmol/kg administered 24 h before MCAO), and the other 3 groups received ZnPPIX followed by 10, 20, and 50 mg/kg/h propofol respectively. At 24 hours of reperfusion, neurological examinations were performed, and after neurological test, brain infarct size and volume, neuronal apoptosis, the level of HO-1 protein expression and HO-1 activity were observed in each group. RESULTS:Propofol significantly improved neurological deficits, reduced infarct volume, and attenuated neuron apoptosis compared with MCAO group alone. Increased HO-1 protein expression was observed in the ischemic penumbra and core of propofol group after transient MCAO. The selective HO-1 activity inhibitor, ZnPPIX, partially eliminated the neuroprotective effects of propofol. CONCLUSIONS: The neuroprotective effects of propofol postconditioning in brain ischemia/reperfusion injury may be partially through the induction of the HO-1 expression.
Authors: Nicholas V Mendez; Jeffrey A Wharton; Jenna L Leclerc; Spiros L Blackburn; Martha V Douglas-Escobar; Michael D Weiss; Christoph N Seubert; Sylvain Doré Journal: Int J Clin Anesthesiol Date: 2013-09-29