• Hailin Zhao, Sian Mitchell, Stefania Koumpa, Yushi Tracy Cui, Qingquan Lian, Henrik Hagberg, Mark R Johnson, Masao Takata, and Daqing Ma.
• From the Faculty of Medicine, Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom (H.Z., S.M., S.K., Y.T.C., M.T., D.M.); Department of Anesthesiology, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China (Q.L.); Division of Imaging Sciences and Biomedical Engineering, Centre for the Developing Brain, King's College London, St. Thomas' Hospital, London, United Kingdom (H.H.); Perinatal Center, Institute of Physiology and Neurosciences and Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (H.H.); and Reproductive Biology, Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom (M.R.J.).
• Anesthesiology. 2016 Jul 1; 125 (1): 180-92.

BackgroundHypoxic-ischemic encephalopathy is a major cause of mortality and disability in the newborn. The authors investigated the protective effects of argon combined with hypothermia on neonatal rat hypoxic-ischemic brain injury.MethodsIn in vitro studies, rat cortical neuronal cell cultures were challenged by oxygen and glucose deprivation for 90 min and exposed to 70% Ar or N2 with 5% CO2 balanced with O2, at 33°C for 2 h. Neuronal phospho-Akt, heme oxygenase-1 and phospho-glycogen synthase kinase-3β expression, and cell death were assessed. In in vivo studies, neonatal rats were subjected to unilateral common carotid artery ligation followed by hypoxia (8% O2 balanced with N2 and CO2) for 90 min. They were exposed to 70% Ar or N2 balanced with oxygen at 33°, 35°, and 37°C for 2 h. Brain injury was assessed at 24 h or 4 weeks after treatment.ResultsIn in vitro studies, argon-hypothermia treatment increased phospho-Akt and heme oxygenase-1 expression and significantly reduced the phospho-glycogen synthase kinase-3β Tyr-216 expression, cytochrome C release, and cell death in oxygen-glucose deprivation-exposed cortical neurons. In in vivo studies, argon-hypothermia treatment decreased hypoxia/ischemia-induced brain infarct size (n = 10) and both caspase-3 and nuclear factor-κB activation in the cortex and hippocampus. It also reduced hippocampal astrocyte activation and proliferation. Inhibition of phosphoinositide-3-kinase (PI3K)/Akt pathway through LY294002 attenuated cerebral protection conferred by argon-hypothermia treatment (n = 8).ConclusionArgon combined with hypothermia provides neuroprotection against cerebral hypoxia-ischemia damage in neonatal rats, which could serve as a new therapeutic strategy against hypoxic-ischemic encephalopathy.

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