Please cite this article in press as: Leger, P.-L., et al., Ischemic postconditioning in cerebral ischemia: Differences between the immature and mature brain? Int. J. Dev. Neurosci. (2015), http://dx.doi.org/10.1016/j.ijdevneu.2015.03.006 ARTICLE IN PRESS G Model DN-1973; No. of Pages 5 Int. J. Devl Neuroscience xxx (2015) xxx–xxx Contents lists available at ScienceDirect International Journal of Developmental Neuroscience j ourna l ho me page: www.elsevier.com/locate/ijdevneu Ischemic postconditioning in cerebral ischemia: Differences between the immature and mature brain? Pierre-Louis Leger a,b,c , Philippe Bonnin d,e , Sylvain Renolleau a,f , Olivier Baud a,b , Christiane Charriaut-Marlangue a,b,∗ a Univ. Paris Diderot, Sorbonne Paris Cité, INSERM UMR 1141, 75019 Paris, France b PremUp Foundation, 75006 Paris, France c UPMC-Paris6, AP-HP, Hôpital Armand Trousseau, Service de Réanimation Néonatale et Pédiatrique, 75012 Paris, France d Univ. Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Lariboisière, Physiologie Clinique, Explorations-Fonctionnelles, 75010 Paris, France e Univ. Paris Diderot, Sorbonne Paris Cité, INSERM, U965, 75010 Paris, France f Univ. Paris Descartes, AP-HP, CHU Necker-Enfants Malades, Réanimation et USC médico-chirurgicales pédiatriques, 75015 Paris, France a r t i c l e i n f o Article history: Received 14 January 2015 Received in revised form 12 March 2015 Accepted 12 March 2015 Available online xxx Keywords: Collateral recruitment Acidosis Reperfusion Hyperemia NO-dependent vascular tone a b s t r a c t Ischemic postconditioning (postC), defined as serial mechanical interruptions of blood flow at reperfu- sion, effectively reduces myocardial infarct size in all species tested so far, including humans. In the brain, ischemic postC leads to controversial results regardless of variations in factors such as onset time of begin- ning, the duration of ischemia and/or reperfusion, and the number of cycles of occlusion/reperfusion. Thus, many major issues remain to be resolved regarding its protective effects. Future studies should aim to identify the parameters that yield the strongest protection, as well as to understand why the efficacy of ischemic postC differs between models. This review will focus on initial hemodynamic changes and their consequences, and on specific features such as NO-dependent vascular tone and/or prolonged acidosis in cerebral ischemia-reperfusion in order to better understand the dynamics of ischemic postC in the developing brain. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction The term “postconditioning” (postC) was first introduced in 1996 by Na et al. (Na et al., 1996). Zhao et al. were the firsts to report the application of postC to limit reperfusion injury in exper- imental acute myocardial infarction (Zhao et al., 2003). Ischemic postC combining brief periods of ischemia alternating with brief periods of re-flow applied at the onset of reperfusion following sustained ischemia effectively reduces myocardial infarct size in all species tested, including humans (Ovize et al., 2010; Staat et al., 2005). Interest in this field has been rekindled with several studies suggesting that postC might reduce injury to organs other than the heart, such as the brain (Zhao et al., 2006) and the kidney (Sun et al., 2004). A Number of reviews has been published in the last few years, but while most of them have focused on signaling pathways ∗ Corresponding author at: INSERM U1141, Hopital Robert Debré, 48 bd Serurier, 75019 Paris, France. Tel.: +33 1 40 03 19 82; fax: +33 1 40 03 19 95. E-mail address: christiane.marlangue@gmail.com (C. Charriaut-Marlangue). induced by ischemic postC–we refer the reader to the excellent review by Zhao et al. (Zhao, 2009)–here we will discuss about early physiological parameters that could account for successful or unsuccessful postC in experimental models of cerebral ischemia. For translation to humans in cardiology, the recommended algo- rithm for postC and protection takes into account at least 3 factors: the delay after which the first re-occlusion is established; the dura- tion and number of re-occlusion; and the duration of interspersed reperfusion (Ovize et al., 2010). A similar postC algorithm [time onset of occlusion, duration of occlusion and/or reperfusion, and number of cycles (Ovize et al., 2010)] has also been evaluated In cerebral ischemia, but has yielded contradictory effects, suggest- ing that specific and timing cell death features differ according to the different models used, and/or the developmental stage, leading to efficiency or not by using a same postC protocol. The effective- ness or ineffectiveness of the postC algorithm could depend on i) the patency of collaterals, ii) NO-dependent vascular tone, and iii) intracellular acidosis. Knowledge of these intrinsic anatomi- cal, functional and physiological features, which vary from one model to another, even in the same species, should improve our http://dx.doi.org/10.1016/j.ijdevneu.2015.03.006 0736-5748/© 2015 Elsevier Ltd. All rights reserved.