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BMC Physiology

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Open Access 01-12-2009 | Research article

Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2

Authors: Yajun Liu, Lianbi Chen, Xiaoqun Xu, Eric Vicaut, Richard Sercombe

Published in: BMC Physiology | Issue 1/2009

Abstract

Background

A major endogenous protective mechanism in many organs against ischemia/reperfusion (I/R) injury is ischemic preconditioning (IPC). By moderately uncoupling the mitochondrial respiratory chain and decreasing production of reactive oxygen species (ROS), IPC reduces apoptosis induced by I/R by reducing cytochrome c release from the mitochondria. One element believed to contribute to reduce ROS production is the uncoupling protein UCP2 (and UCP3 in the heart). Although its implication in IPC in the brain has been shown in vitro, no in vivo study of protein has shown its upregulation. Our first goal was to determine in rat hippocampus whether UCP2 protein upregulation was associated with IPC-induced protection and increased ROS production. The second goal was to determine whether the peptide ghrelin, which possesses anti-oxidant and protective properties, alters UCP2 mRNA levels in the same way as IPC during protection.

Results

After global forebrain ischemia (15 min) with 72 h reperfusion (I/R group), we found important neuronal lesion in the rat hippocampal CA1 region, which was reduced by a preceding 3-min preconditioning ischemia (IPC+I/R group), whereas the preconditioning stimulus alone (IPC group) had no effect. Compared to control, UCP2 protein labelling increased moderately in the I/R (+39%, NS) and IPC+I/R (+28%, NS) groups, and substantially in the IPC group (+339%, P < 0.05). Treatment with superoxide dismutase (10000 U/kg ip) at the time of a preconditioning ischemia greatly attenuated (-73%, P < 0.001) the increase in UCP2 staining at 72 h, implying a role of oxygen radicals in UCP2 induction.

Hippocampal UCP2 mRNA showed a moderate increase in I/R (+33%, P < 0.05) and IPC+I/R (+40%, P < 0.05) groups versus control, and a large increase in the IPC group (+333%, P < 0.001). In ghrelin experiments, the I/R+ghrelin group (3 daily administrations) showed considerable protection of CA1 neurons versus I/R animals, and increased hippocampal UCP2 mRNA (+151%, P < 0.001).

Conclusion

We confirm that IPC causes increased expression of UCP2 protein in vivo, at a moment appropriate for protection against I/R in the hippocampus. The two dissimilar protective strategies, IPC and ghrelin administration, were both associated with upregulated UCP2, suggesting that UCP2 may often represent a final common pathway in protection from I/R.

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Title: Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2
Authors: Yajun Liu
Lianbi Chen
Xiaoqun Xu
Eric Vicaut
Richard Sercombe
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: BMC Physiology / Issue 1/2009
Electronic ISSN: 1472-6793
DOI: https://doi.org/10.1186/1472-6793-9-17

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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