naa a22 4500 510775640 CHVBK 20180411083229.0 cr unu---uuuuu 180411e20130201xx s 000 0 eng 10.1007/s12975-012-0224-3 doi (NATIONALLICENCE)springer-10.1007/s12975-012-0224-3 Clinical Application of Preconditioning and Postconditioning to Achieve Neuroprotection [Elektronische Daten] [Cameron Dezfulian, Matthew Garrett, Nestor Gonzalez] Ischemic conditioning is a form of endogenous protection induced by transient, subcritical ischemia in a tissue. Organs with high sensitivity to ischemia, such as the heart, the brain, and spinal cord, represent the most critical and potentially promising targets for potential therapeutic applications of ischemic conditioning. Numerous preclinical investigations have systematically studied the molecular pathways and potential benefits of both pre- and postconditioning with promising results. The purpose of this review is to summarize the present knowledge on cerebral pre- and postconditioning, with an emphasis in the clinical application of these forms of neuroprotection. A systematic MEDLINE search for the terms preconditioning and postconditioning was performed. Publications related to the nervous system and to human applications were selected and analyzed. Pre- and postconditioning appear to provide similar levels of neuroprotection. The preconditioning window of benefit can be subdivided into early and late effects, depending on whether the effect appears immediately after the sublethal stress or with a delay of days. In general, early effects have been associated posttranslational modification of critical proteins (membrane receptors, mitochondrial respiratory chain) while late effects are the result of gene up- or downregulation. Transient ischemic attacks appear to represent a form of clinically relevant preconditioning by inducing ischemic tolerance in the brain and reducing the severity of subsequent strokes. Remote forms of ischemic pre- and postconditioning have been more commonly used in clinical studies, as the remote application reduces the risk of injuring the target tissue for which protection is pursued. Limb transient ischemia is the preferred method of induction of remote conditioning with evidence supporting its safety. Clinical studies in a variety of populations at risk of central nervous damage including carotid disease, cervical myelopathy, and subarachnoid hemorrhage have shown improvement in surrogate markers of injury. Promising preclinical and early clinical studies noting improvement in surrogate markers of central nervous injury after the use of remote pre- and postconditioning treatments demand follow-up systematic investigations to address effectiveness. Challenges in the application of these techniques to pressing clinical cerebrovascular disease ought to be overcome through careful, well-designed, translational investigations. Springer Science+Business Media New York, 2012 Preconditioning nationallicence Postconditioning nationallicence Ischemia nationallicence Reperfusion injury nationallicence Neuroprotection nationallicence Brain injury nationallicence Dezfulian Cameron Department of Critical Care Medicine, Safar Center for Resuscitation Research, Vascular Medicine Institute, University of Pittsburgh School of Medicine, 100 Hill Building, 3434 Fifth Avenue, 15260, Pittsburgh, PA, USA aut Garrett Matthew David Geffen School of Medicine at UCLA, Los Angeles, CA, USA aut Gonzalez Nestor David Geffen School of Medicine at UCLA, Los Angeles, CA, USA aut Translational Stroke Research Springer US; http://www.springer-ny.com 4/1(2013-02-01), 19-24 1868-4483 4:1<19 2013 4 12975 https://doi.org/10.1007/s12975-012-0224-3 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-012-0224-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dezfulian Cameron Department of Critical Care Medicine, Safar Center for Resuscitation Research, Vascular Medicine Institute, University of Pittsburgh School of Medicine, 100 Hill Building, 3434 Fifth Avenue, 15260, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Garrett Matthew David Geffen School of Medicine at UCLA, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Gonzalez Nestor David Geffen School of Medicine at UCLA, Los Angeles, CA, USA aut NATIONALLICENCE 773 0- Translational Stroke Research Springer US; http://www.springer-ny.com 4/1(2013-02-01), 19-24 1868-4483 4:1<19 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer