title: Immune mechanisms in cerebral ischemic tolerance.
abstract: 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.
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College New York, NY, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Garcia-Bonilla
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College New York, NY, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Benakis
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College New York, NY, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Moore
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College New York, NY, USA.
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
authors.affiliation: Brain and Mind Research Institute, Weill Cornell Medical College New York, NY, USA.
authors.forename: Josef
authors.initials: J
authors.lastname: Anrather
keywords: TLR; TNF; epigenetics; inflammation; ischemic tolerance; microRNAs; preconditioning; stroke