Ischemic preconditioning protects hippocampal pyramidal neurons from transient ischemic injury via the attenuation of oxidative damage through upregulating heme oxygenase-1.
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| 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.
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| Authors | Jae-Chul Lee, In Hye Kim, Joon Ha Park, Ji Hyeon Ahn, Jeong-Hwi Cho, Geum-Sil Cho, Hyun-Jin Tae, Bai Hui Chen, Bing Chun Yan, Ki-Yeon Yoo, Jung Hoon Choi, Choong Hyun Lee, In Koo Hwang, Jun Hwi Cho, Young-Guen Kwon, Young-Myeong Kim, Moo-Ho Won |
| Journal | Free radical biology & medicine (Free Radic Biol Med) Vol. 79 Pg. 78-90 (Feb 2015) ISSN: 1873-4596 [Electronic] United States |
| PMID | 25483558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
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