title: Helium preconditioning protects against neonatal hypoxia-ischemia via nitric oxide mediated up-regulation of antioxidases in a rat model.
abstract: This study aimed to investigate the role of nitric oxide (NO) in the neuroprotective effects of helium preconditioning (He-PC) in a neonatal hypoxia/ischemia (HI) rat model. Seven-day old rat pups were divided into normal control group, He-PC group, HI group, He-PC+HI group, L-NAME+HI group and L-NAME+He-PC+HI group. HI was induced by exposure to 80% oxygen for 90 min. He-PC was conducted with 70% helium-30% oxygen for three 5-min periods. Three hours after He-PC, animals in control group and He-PC group were sacrificed, and the brain was collected for the detection of NO content. At 24h after HI, animals in control group, HI group, He-PC+HI group, and L-NAME+He-PC+HI group were sacrificed, and the brain was collected for detection of infarct ratio, antioxidases (SOD, HO-1 and Nrf2), DNA binding activity of Nrf2 and TUNEL staining. Three weeks later, the neurological function and brain atrophy were determined. Results showed pretreatment with L-NAME alone failed to exert protective effect on HI. He-PC significantly increased NO content, reduced the brain infarct area, increased anti-oxidases expression and DNA binding activity of Nrf2, decreased the apoptotic cells, and improved the neurological function and brain atrophy. In addition, this protection was markedly inhibited by L-NAME (a non-selective NOS inhibitor). These findings suggest that the He-PC may induce NO production to activate Nrf2, exerting neuroprotective effect on neonatal HI.
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Diving and Hyperbaric Medicine, Secondary Military Medical University, No 800, Xiangyin Road, Yangpu District, Shanghai 200433, China.
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Diving and Hyperbaric Medicine, Secondary Military Medical University, No 800, Xiangyin Road, Yangpu District, Shanghai 200433, China.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Kang
authors.affiliation: Department of Diving and Hyperbaric Medicine, Secondary Military Medical University, No 800, Xiangyin Road, Yangpu District, Shanghai 200433, China.
authors.forename: X J
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Department of Diving and Hyperbaric Medicine, Secondary Military Medical University, No 800, Xiangyin Road, Yangpu District, Shanghai 200433, China. Electronic address: liuwenwu1980@hotmail.com.
authors.forename: W W
authors.initials: WW
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China. Electronic address: maoyanfei1979@163.com.
authors.forename: Y F
authors.initials: YF
authors.lastname: Mao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006371:Helium / Q000008:administration & dosage*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D009043:Motor Activity / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D006371:Helium; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester
keywords: Antioxidase; Helium preconditioning; Neonatal rats; Neuroprotection; Nitric oxide