التفاصيل البيبلوغرافية
| العنوان: |
Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke. |
| المؤلفون: |
Spescha, R. D., Klohs, J., Semerano, A., Giacalone, G., Derungs, R. S., Reiner, M. F., Gutierrez, D. Rodriguez, Mendez-Carmona, N., Glanzmann, M., Savarese, G., Kränkel, N., Akhmedov, A., Keller, S., Mocharla, P., Kaufmann, M. R., Wenger, R. H., Vogel, J., Kulic, L., Nitsch, R. M., Beer, J. H. |
| المصدر: |
European Heart Journal; Jul2015, Vol. 36 Issue 25, p1590-1600a, 12p, 2 Charts, 5 Graphs |
| مستخلص: |
Aim Constitutive genetic deletion of the adaptor protein p66Shc was shown to protect from ischaemia/reperfusion injury. Here, we aimed at understanding the molecular mechanisms underlying this effect in stroke and studied p66Shc gene regulation in human ischaemic stroke. Methods and results Ischaemia/reperfusion brain injury was induced by performing a transient middle cerebral artery occlusion surgery on wild-type mice. After the ischaemic episode and upon reperfusion, small interfering RNA targeting p66Shc was injected intravenously. We observed that post-ischaemic p66Shc knockdown preserved blood-brain barrier integrity that resulted in improved stroke outcome, as identified by smaller lesion volumes, decreased neurological deficits, and increased survival. Experiments on primary human brain microvascular endothelial cells demonstrated that silencing of the adaptor protein p66Shc preserves claudin-5 protein levels during hypoxia/reoxygenation by reducing nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production. Further, we found that in peripheral blood monocytes of acute ischaemic stroke patients p66Shc gene expression is transiently increased and that this increase correlates with short-term neurological outcome. Conclusion Post-ischaemic silencing of p66Shc upon reperfusion improves stroke outcome in mice while the expression of p66Shc gene correlates with short-term outcome in patients with ischaemic stroke. [ABSTRACT FROM AUTHOR] |
|
Copyright of European Heart Journal is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder