NCX as a Key Player in the Neuroprotection Exerted by Ischemic Preconditioning and Postconditioning

  • Giuseppe Pignataro
  • Ornella Cuomo
  • Antonio Vinciguerra
  • Rossana Sirabella
  • Elga Esposito
  • Francesca Boscia
  • Gianfranco Di Renzo
  • Lucio AnnunziatoEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 961)


Ischemic preconditioning is a neuroprotective mechanism in which a brief non-injurious episode of ischemia protects the brain from a subsequent lethal insult. Recently, it has been reported that modified reperfusion subsequent to a prolonged ischemic episode may also confer neuroprotection, a phenomenon termed postconditioning. Mitogen-activated protein kinases (MAPK) play a key role in these two neuroprotective mechanisms. The aim of this study was to evaluate whether Na+/Ca2+ exchangers (NCXs), a family of ionic transporters that contribute to the maintenance of intracellular ionic homeostasis, contribute to the neuroprotection elicited by ischemic preconditioning and postconditioning.

Results of this study indicated that (1) NCX1 and NCX3 are upregulated in those brain regions protected by preconditioning, while (2) postconditioning treatment induces an upregulation only in NCX3 expression. (3) NCX1 upregulation and NCX3 upregulation are mediated by p-AKT since its inhibition reverted the neuroprotective effect of preconditioning and postconditioning and prevented NCXs overexpression. (4) The involvement of NCX in preconditioning and postconditioning neuroprotection is further supported by the results of experiments showing that a partial reversion of the protective effect induced by preconditioning was obtained by silencing NCX1 or NCX3, while the silencing of NCX3 was able to mitigate the protection induced by ischemic postconditioning.

Altogether, the data presented here suggest that NCX1 and NCX3 ­represent two promising druggable targets for setting on new strategies in stroke therapy.


Preconditioning Postconditioning NCX1 NCX3 p-AKT 



This work was supported by COFIN 2008; Ricerca-Sanitaria RF-FSL352059 Ricerca finalizzata 2006; Ricerca-Oncologica 2006; Progetto-Strategico 2007; Progetto Ordinario 2007; Ricerca finalizzata 2009; Ricerca-Sanitaria Progetto Ordinario by Ministero della Salute 2008 all to LA.

The authors thank:

1.Elsevier for permission of using Figs. 19.1 and 19.2, license number 2821360173915, and three excerpts, license number 2821360363363, from the article that appeared in Neurobiology of Disease, 2012, by Pignataro G. et al.

2.John Wiley and Sons for permission of using text extracts from the article that appeared in FEBS Journal, 2009, by Pignataro G. et al.

3.Nature Publishing Group for permission of using text extracts and Figs. 19.3 and 19.4 from the article that appeared in Journal of Cerebral Blood Flow and Metabolism, 2011, by Pignataro G. et al.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Giuseppe Pignataro
    • 1
  • Ornella Cuomo
    • 1
  • Antonio Vinciguerra
    • 1
  • Rossana Sirabella
    • 2
  • Elga Esposito
    • 1
  • Francesca Boscia
    • 1
  • Gianfranco Di Renzo
    • 1
  • Lucio Annunziato
    • 1
    Email author
  1. 1.Division Pharmacology, Department Neuroscience, School of MedicineFederico II University of NaplesNaplesItaly
  2. 2.Fondazione IRCCS SDNNaplesItaly

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