A critical review of mechanisms regulating remote preconditioning-induced brain protection.

Remote preconditioning (rPC) is the phenomenon whereby brief organ ischemia evokes an endogenous response such that a different (remote) organ is protected against subsequent, normally injurious ischemia. Experiments show rPC to be effective at evoking cardioprotection against ischemic heart injury and, more recently, neuroprotection against brain ischemia. Such is the enthusiasm for rPC that human studies have been initiated. Clinical trials suggest rPC to be safe (phase II trial) and effective in reducing stroke incidence in a population with high stroke risk. However, despite the therapeutic potential of rPC, there is a large gap in knowledge regarding the effector mechanisms of rPC and how it might be orchestrated to improve outcome after stroke. Here we provide a critical review of mechanisms that are directly attributable to rPC-induced neuroprotection in preclinical trials of rPC.