Ischemic Tolerance: The Mechanisms of Neuroprotective Strategy

The phenomenon of ischemic tolerance perfectly describes this quote “What does not kill you makes you stronger.” Ischemic pre‐ or postconditioning is actually the strongest known procedure to prevent or reverse neurodegeneration. It works specifically in sensitive vulnerable neuronal populations, which are represented by pyramidal neurons in the hippocampal CA1 region. However, tolerance is effective in other brain cell populations as well. Although, its nomenclature is “ischemic” tolerance, the tolerant phenotype can also be induced by other stimuli that lead to delayed neuronal death (intoxication). Moreover, the recent data have proven that this phenomenon is not limited to application of sublethal stimuli before the lethal stress but reversed arrangement of events, sublethal stress after lethal insult, is rather equally effective. A very important term is called “cross conditioning.” Cross conditioning is the capability of one stressor to induce tolerance against another. So, since pre‐ or post‐conditioners can be used plenty of harmful stimuli, hypo‐ or hyperthermia and some physiological compounds, such as norepinephrine, bradykinin. Delayed neuronal death is the slow development of postischemic neurodegeneration. This allows an opportunity for a great therapeutic window of 2–3 days to reverse the cellular death process. Moreover, it seems that the mechanisms of ischemic tolerance‐delayed postconditioning could be used not only after ischemia but also in some other processes leading to apoptosis. Anat Rec, 292:2002–2012, 2009. © 2009 Wiley‐Liss, Inc.