The first two authors contributed equally to this work.
Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack
Article first published online: 23 NOV 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 83, Issue 1, pages 19–27, January 2006
How to Cite
Malhotra, S., Savitz, S. I., Ocava, L. and Rosenbaum, D. M. (2006), Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack. J. Neurosci. Res., 83: 19–27. doi: 10.1002/jnr.20705
- Issue published online: 21 DEC 2005
- Article first published online: 23 NOV 2005
- Manuscript Revised: 30 SEP 2005
- Manuscript Accepted: 30 SEP 2005
- Manuscript Received: 2 SEP 2005
- NIH. Grant Number: EY11253
- AHA Fellow
- ischemic preconditioning;
- PI-3 kinase;
Ischemic preconditioning (IP) protects the brain from subsequent, prolonged, and lethal ischemia in experimental studies. Erythropoietin (EPO) participates in the brain's intrinsic response to injury and may play a role in preconditioning. By using a middle cerebral artery occlusion (MCAo) model of transient ischemic attack (TIA), we sought to determine whether EPO is required for IP in the protective response against focal ischemic stroke. Rats underwent three 10-min MCA occlusions or sham surgery. Three days later, animals underwent 2 hr of MCAo and 22 hr of reperfusion. Experimental TIAs reduced infarct volumes by 55% (P < 0.05), inhibited DNA fragmentation, and improved neurological outcome by 50% (P < 0.05) after ischemic stroke. EPO and its receptor were up-regulated by IP in the ipsilateral hemisphere by 24 hr after IP, before ischemic stroke and soluble EPO receptor attenuated neuroprotection by IP (88% reduction, P < 0.05). Pretreatment with the PI-3 kinase inhibitor wortmannin abolished the protective effect of IP against ischemic injury (P < 0.05). IP may be mediated in part by EPO through a PI-3 kinase pathway. © 2005 Wiley-Liss, Inc.