title: Effects of ischemic preconditioning on VEGF and pFlk-1 immunoreactivities in the gerbil ischemic hippocampus after transient cerebral ischemia.
abstract: Ischemia preconditioning (IPC) displays an important adaptation of the CNS to sub-lethal ischemia. In the present study, we examined the effect of IPC on immunoreactivities of VEGF-, and phospho-Flk-1 (pFlk-1) following transient cerebral ischemia in gerbils. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+) sham-operated-group, and IPC+ischemia-operated-group). IPC was induced by subjecting gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated-group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) alone 5 days after ischemia-reperfusion, however, in all the IPC+ischemia-operated-groups, pyramidal neurons in the SP were well protected. In immunohistochemical study, VEGF immunoreactivity in the ischemia-operated-group was increased in the SP at 1 day post-ischemia and decreased with time. Five days after ischemia-reperfusion, strong VEGF immunoreactivity was found in non-pyramidal cells, which were identified as pericytes, in the stratum oriens (SO) and radiatum (SR). In the IPC+sham-operated- and IPC+ischemia-operated-groups, VEGF immunoreactivity was significantly increased in the SP. pFlk-1 immunoreactivity in the sham-operated- and ischemia-operated-groups was hardly found in the SP, and, from 2 days post-ischemia, pFlk-1 immunoreactivity was strongly increased in non-pyramidal cells, which were identified as pericytes. In the IPC+sham-operated-group, pFlk-1 immunoreactivity was significantly increased in both pyramidal and non-pyramidal cells; in the IPC+ischemia-operated-groups, the similar pattern of VEGF immunoreactivity was found in the ischemic CA1, although the VEGF immunoreactivity was strong in non-pyramidal cells at 5 days post-ischemia. In brief, our findings show that IPC dramatically augmented the induction of VEGF and pFlk-1 immunoreactivity in the pyramidal cells of the CA1 after ischemia-reperfusion, and these findings suggest that the increases of VEGF and Flk-1 expressions may be necessary for neurons to survive from transient ischemic damage.
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Yoo Seok
authors.initials: YS
authors.lastname: Park
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 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 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 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 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 Physiology, College of Medicine and Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Bai Hui
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Department of Physiology, College of Medicine and Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Bich-Na
authors.initials: BN
authors.lastname: Shin
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Myoung Cheol
authors.initials: MC
authors.lastname: Shin
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea; Department of Emergency Medicine, Seoul Hospital, College of Medicine, Sooncheonhyang University, Seoul 140-743, South Korea.
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Physiology, College of Medicine and Institute of Neurodegeneration and Neuroregeneration, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Yun Lyul
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
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
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: anajclee@kangwon.ac.kr.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D017966:Pyramidal Cells / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Delayed neuronal death; Ischemia–reperfusion; Ischemic preconditioning; Pericytes; Phospho-Flk-1; Vascular endothelial growth factor