title: Isoflurane postconditioning improved long-term neurological outcome possibly via inhibiting the mitochondrial permeability transition pore in neonatal rats after brain hypoxia-ischemia.
abstract: BACKGROUND
  Isoflurane postconditioning induces neuroprotection in neonatal rats after hypoxia/ischemia (HI). Here, we evaluated the possible role of inhibiting the mitochondrial permeability transition pore (mPTP) in isoflurane postconditioning-improved long-term neurological outcome after brain HI.
  
  
  METHODS
  Seven-day-old Sprague-Dawley rats (n=360) were randomly divided into eight groups (n=45 in each). They underwent or did not undergo left common carotid arterial ligation followed by exposure to 8% oxygen for 2 h at 37°C (brain HI). The mPTP opener atractyloside or inhibitor cyclosporin A was injected into the lateral cerebral ventricle. The weight ratio and neuronal density ratio in the ventral posteromedial thalamic nucleus and hippocampal CA3 area of left to right cerebral hemispheres were evaluated at 7 or 35 days after brain HI. The changes of mitochondrial optical density (ΔOD540 of mPTP) and the performance in Morris water maze were assessed.
  
  
  RESULTS
  Compared with the control (sham group), brain HI decreased the weight ratio and neuronal density ratio in the ventral posteromedial thalamic nucleus and hippocampal CA3 area (P<0.05). Brain HI also impaired the performance of rats in the Morris water maze and increased the ΔOD540. These effects of brain HI were reduced by isoflurane postconditioning and cyclosporin A. The improvement induced by isoflurane postconditioning was attenuated by atractyloside.
  
  
  CONCLUSIONS
  Isoflurane postconditioning improved long-term neurological functions after brain HI in neonatal rats. Inhibiting the opening of the mPTP may contribute to this protection.
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: zhaoping_cmu2002@yahoo.com.
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: jiguoyu212@126.com.
authors.forename: G
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: xuehang0407@163.com.
authors.forename: H
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: yuweiwei312@163.com.
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: 794491252@qq.com.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: 873570518@qq.com.
authors.forename: M
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: 1055126880@qq.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China; Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, United States. Electronic address: zz3c@virginia.edu.
authors.forename: Z
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001278:Atractyloside / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017536:Carotid Artery, Common; D002491:Central Nervous System Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007530:Isoflurane / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects; D020651:Ventral Thalamic Nuclei / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D002491:Central Nervous System Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents; D001278:Atractyloside; D016572:Cyclosporine; D007530:Isoflurane
keywords: hypoxic/ischemic brain injury; isoflurane; mitochondrial permeability transition pore; neonatal rat; postconditioning