Roles of HIF-1α, VEGF, and NF-κB in Ischemic Preconditioning-Mediated Neuroprotection of Hippocampal CA1 Pyramidal Neurons Against a Subsequent Transient Cerebral Ischemia

Jae Chul Lee, Hyun Jin Tae, In Hye Kim, Jeong Hwi Cho, Tae Kyeong Lee, Joon Ha Park, Ji Hyeon Ahn, Soo Young Choi, Hui Chen Bai, Bich Na Shin, Geum Sil Cho, Dae Won Kim, Il Jun Kang, Young Guen Kwon, Young Myeong Kim, Moo Ho Won, Eun Joo Bae

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Abstract

Ischemic preconditioning (IPC) provides neuroprotection against subsequent severe ischemic insults by specific mechanisms. We tested the hypothesis that IPC attenuates post-ischemic neuronal death in the gerbil hippocampal CA1 region (CA1) throughout hypoxia inducible factor-1α (HIF-1α) and its associated factors such as vascular endothelial growth factor (VEGF) and nuclear factor-kappa B (NF-κB). Lethal ischemia (LI) without IPC increased expressions of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) in CA1 pyramidal neurons at 12 h and/or 1-day post-LI; thereafter, their expressions were decreased in the CA1 pyramidal neurons with time and newly expressed in non-pyramidal cells (pericytes), and the CA1 pyramidal neurons were dead at 5-day post-LI, and, at this point in time, their immunoreactivities were newly expressed in pericytes. In animals with IPC subjected to LI (IPC/LI)-group), CA1 pyramidal neurons were well protected, and expressions of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) were significantly increased compared to the sham-group and maintained after LI. Whereas, treatment with 2ME2 (a HIF-1α inhibitor) into the IPC/LI-group did not preserve the IPC-mediated increases of HIF-1α, VEGF, and p-IκB-α (/and translocation of NF-κB p65 into nucleus) expressions and did not show IPC-mediated neuroprotection. In brief, IPC protected CA1 pyramidal neurons from LI by upregulation of HIF-1α, VEGF, and p-IκB-α expressions. This study suggests that IPC increases HIF-1α expression in CA1 pyramidal neurons, which enhances VEGF expression and NF-κB activation and that IPC may be a strategy for a therapeutic intervention of cerebral ischemic injury.

Original languageEnglish
Pages (from-to)6984-6998
Number of pages15
JournalMolecular Neurobiology
Volume54
Issue number9
DOIs
Publication statusPublished - 2017 Nov 1

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All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Lee, J. C., Tae, H. J., Kim, I. H., Cho, J. H., Lee, T. K., Park, J. H., Ahn, J. H., Choi, S. Y., Bai, H. C., Shin, B. N., Cho, G. S., Kim, D. W., Kang, I. J., Kwon, Y. G., Kim, Y. M., Won, M. H., & Bae, E. J. (2017). Roles of HIF-1α, VEGF, and NF-κB in Ischemic Preconditioning-Mediated Neuroprotection of Hippocampal CA1 Pyramidal Neurons Against a Subsequent Transient Cerebral Ischemia. Molecular Neurobiology, 54(9), 6984-6998. https://doi.org/10.1007/s12035-016-0219-2