title: Sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway.
abstract: BACKGROUND
  Volatile anesthetic postconditioning has been documented to provide neuroprotection in adult animals. Our aim was to investigate whether sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage (HIBD) rats, and whether the PI3K/Akt pathway and mitochondrial permeability transition pore (mPTP) opening participate in the effect.
  
  
  METHODS
  Seven-day-old Sprague-Dawley rats were subjected to brain HI and randomly allocated to 10 groups (n=24 each group) and treated as follows: (1) Sham, without hypoxia-ischemia; (2) HI/Control, received cerebral hypoxia-ischemia; (3) HI+Atractyloside (Atr), (4) HI+Cyclosporin A (CsA), (5) HI+sevoflurane (Sev), (6) HI+Sev+ LY294002 (LY), (7) HI+Sev+ L-NAME (L-N), (8) HI+Sev+ SB216763 (SB), (9) HI+Sev+Atr, and (10) HI+Sev+CsA. Twelve rats in each group underwent behavioral testing and their brains were harvested for hippocampus neuron count and morphology study. Brains of the other 12 animals were harvested 24h after intervention to examine the expression of Akt, p-Akt, eNOS, p-eNOS, GSK-3β, p-GSK-3β by Western bolting and mPTP opening.
  
  
  RESULTS
  Sevoflurane postconditioning significantly improved the long-term cognitive performance of the rats, increased the number of surviving neurons in CA1 and CA3 hippocampal regions, and protected the histomorphology of the left hippocampus. These effects were abolished by inhibitors of PI3K/eNOS/GSK-3β. Although blocking mPTP opening simulated sevoflurane postconditioning-induced neuroprotection, it failed to enhance it.
  
  
  CONCLUSIONS
  Sevoflurane postconditioning exerts a neuroprotective effect against HIBD in neonatal rats via PI3K/Akt/eNOS and PI3K/Akt/GSK-3β pathways, and blockage of mPTP opening may be involved in attenuation of histomorphological injury.
authors.affiliation: Deparment of Anesthesiology, Fujian Medical University Union Hospital, 29 Xin-Quan Road, Fuzhou 350001, PR China. Electronic address: guodh1981@163.com.
authors.forename: Zhongmeng
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Deparment of Anesthesiology, Fujian Medical University Union Hospital, 29 Xin-Quan Road, Fuzhou 350001, PR China. Electronic address: zhanglc6@163.com.
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Deparment of Anesthesiology, Fujian Medical University Union Hospital, 29 Xin-Quan Road, Fuzhou 350001, PR China. Electronic address: sjs2028@163.com.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Su
authors.affiliation: Deparment of Anesthesiology, The First Affiliated Hospital of Xiamen University, 55 Zhen-Hai Road, Xiamen 3610003, PR China. Electronic address: caidongmiao@hotmail.com.
authors.forename: Dongmiao
authors.initials: D
authors.lastname: Cai
authors.affiliation: Deparment of Anesthesiology, Fujian Medical University Union Hospital, 29 Xin-Quan Road, Fuzhou 350001, PR China. Electronic address: 18201019@qq.com.
authors.forename: Qingxiu
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D057775:Ischemic Postconditioning / Q000379:methods*; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D008738:Methyl Ethers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077149:Sevoflurane
keywords: Hypoxic-ischemic brain damage; Long-term learning and memory; Mitochondrial permeability transition pore; Neonatal rat; PI3K/Akt pathway; Sevoflurane postconditioning