Cerebral preconditioning and ischaemic tolerance

Abstract

Adaptation is one of physiology's fundamental tenets, operating not only at the level of species, as Darwin proposed, but also at the level of tissues, cells, molecules and, perhaps, genes. During recent years, stroke neurobiologists have advanced a considerable body of evidence supporting the hypothesis that, with experimental coaxing, the mammalian brain can adapt to injurious insults such as cerebral ischaemia to promote cell survival in the face of subsequent injury. Establishing this protective phenotype in response to stress depends on a coordinated response at the genomic, molecular, cellular and tissue levels. Here, I summarize our current understanding of how 'preconditioning' stimuli trigger a cerebroprotective state known as cerebral 'ischaemic tolerance'.

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

“…Many exogenously delivered chemical preconditioning agents (eg, inflammatory cytokines, anesthetics, and metabolic inhibitors) can also induce ischemic tolerance, raising the hope that in the future, IPC and postconditioning could be pharmacologically mimicked in vivo. 13 Therefore, the present results support that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in DR treatment.…”

“…11,12 Ischemic preconditioning requires a brief period of ischemia applied before ischemic injury, which does not produce any damage per se, and triggers yet incompletely described mechanisms that result in tolerance to the subsequent severely damaging ischemic event. 13 It was shown that IPC affords the retina a greater degree of protection against ischemic damage than any known neuroprotective agent. 11 Moreover, clinical studies support the effectiveness of IPC in the brain of humans with transient ischemic attacks.…”

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

“…Preconditioning refers to a mildly injurious event that confers protection against a later, more injurious, event (Gidday 2006;Dirnagl et al 2003;Eisen et al 2004;Ran et al 2005). Demonstrated preconditioning inducers against NIPTS in mice include mild noise, heat stress, restraint, and hypoxia (Yoshida et al 1999;Wang and Liberman 2002;Yoshida and Liberman 2000;Niu and Canlon 2002;Gagnon et al 2007).…”

The effect of thrombin on a 6-hydroxydopamine model of Parkinson's disease depends on timing

“…It is well established that a minor insult to the brain can activate cell survival mechanisms that can reduce or prevent tissue destruction normally expected from a severe insult several days later [15]. In ischemia models, resistance to an otherwise major cereberovascular challenge has been called "ischemic tolerance".…”

“…Such cross-tolerance among other injury models is known to occur [15]. Although the mechanisms of protection remain to be determined, the preconditioning effects of thrombin depend on activation of the protease-activated receptor-1 (PAR-1) [4], a thrombin receptor linked to injury tolerance [21].…”