title: Ischemic preconditioning protects hippocampal pyramidal neurons from transient ischemic injury via the attenuation of oxidative damage through upregulating heme oxygenase-1.
abstract: Ischemic preconditioning (IPC) provides neuroprotection against subsequent severe ischemic injury by activating specific mechanisms. In this study, we tested the hypothesis that IPC attenuates postischemic neuronal death via heme oxygenase-1 (HO-1). Animals used in this study were randomly assigned to 4 groups; sham-operated group, ischemia-operated group, IPC plus (+) sham-operated group and IPC+ischemia-operated group. IPC was induced by subjecting gerbils to 2min of ischemia followed by 1 day of recovery. A significant loss of neurons was observed in pyramidal neurons of the hippocampal CA1 region (CA1) in the ischemia-operated groups at 5 days postischemia. In the IPC+ischemia-operated groups, CA1 pyramidal neurons were well protected. The level of HO-1 protein and its activity increased significantly in the CA1 of the IPC+sham-operated group, and the level and activity was maintained in all the time after ischemia-reperfusion compared with the ischemia-operated groups. HO-1 immunoreactivity was induced in the CA1 pyramidal neurons in both IPC+sham-operated- and IPC+ischemia-operated groups. We also found that levels or immunoreactivities of superoxide anion, 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal were significantly decreased in the CA1 of both IPC+sham-operated- and IPC+ischemia-operated groups. Whereas, treatment with zinc protoporphyrin IX (a HO-1 inhibitor) into the IPC+ischemia-operated groups did not preserve the IPC-mediated increase of HO-1 and lost beneficial effects of IPC by inhibiting ischemia-induced DNA damage and lipid peroxidation. In brief, IPC protects CA1 pyramidal neurons from ischemic injury by upregulating HO-1, and we suggest that the enhancement of HO-1 expression by IPC may be a legitimate strategy for a therapeutic intervention of cerebral ischemic damage.
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jeong-Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neuroscience, College of Medicine, Korea University, Seoul 136-705, South Korea.
authors.forename: Geum-Sil
authors.initials: GS
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Bai Hui
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Institute of Integrative Traditional & Western Medicine & Medical College, Yangzhou University, Yangzhou 225-001, China.
authors.forename: Bing Chun
authors.initials: BC
authors.lastname: Yan
authors.affiliation: Department of Oral Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, South Korea.
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.affiliation: Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, South Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: ymkim@kangwon.ac.kr.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D056547:CA1 Region, Hippocampal / Q000201:enzymology / Q000473:pathology*; D005849:Gerbillinae; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D018384:Oxidative Stress; D015854:Up-Regulation
chemical_list: D051547:Heme Oxygenase-1
keywords: Delayed neuronal death; Heme oxygenase-1; Ischemia–reperfusion; Ischemic preconditioning; Oxidative stress