Pharmacologic preconditioning: translating the promise.

A transient, ischemia-resistant phenotype known as "ischemic tolerance" can be established in brain in a rapid or delayed fashion by a preceding noninjurious "preconditioning" stimulus. Initial preclinical studies of this phenomenon relied primarily on brief periods of ischemia or hypoxia as preconditioning stimuli, but it was later realized that many other stressors, including pharmacologic ones, are also effective. This review highlights the surprisingly wide variety of drugs now known to promote ischemic tolerance, documented and to some extent mechanistically characterized in preclinical animal models of stroke. Although considerably more experimentation is needed to thoroughly validate the ability of any currently identified preconditioning agent to protect ischemic brain, the fact that some of these drugs are already clinically approved for other indications implies that the growing enthusiasm for translational success in the field of pharmacologic preconditioning may be well justified.