Impact Factor
This article is part of the Research Topic Brain-immune interactions in health and disease


Front. Neurosci., 04 March 2014 | http://dx.doi.org/10.3389/fnins.2014.00044

Immune mechanisms in cerebral ischemic tolerance

  • Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA

Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance). These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning) can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance (IT) in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral IT acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish IT and that IT can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of IT and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies.

Keywords: preconditioning, ischemic tolerance, stroke, TLR, epigenetics, microRNAs, TNF, inflammation

Citation: Garcia-Bonilla L, Benakis C, Moore J, Iadecola C and Anrather J (2014) Immune mechanisms in cerebral ischemic tolerance. Front. Neurosci. 8:44. doi: 10.3389/fnins.2014.000

Received: 29 September 2013; Accepted: 17 February 2014;
Published online: 04 March 2014.

Edited by:

Adam Denes, University of Manchester, UK

Reviewed by:

Sophie Layé, Université Bordeaux, France
Craig J. Smith, Salford Royal NHS Foundation Trust, UK

Copyright © 2014 Garcia-Bonilla, Benakis, Moore, Iadecola and Anrather. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Josef Anrather, Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street, RR-409, New York, NY 10065, USA e-mail: joa2006@med.cornell.edu