Cerebral ischemic preconditioning. An experimental phenomenon or a clinical important entity of stroke prevention?

Neurons can be preconditioned by various procedures to resist ischemic events. The preconditioning mechanism induced is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. The basic molecular mechanisms of ischemic tolerance are largely unknown. During the induction phase N-methyl-O-aspartate and adenosine receptors and, possibly, oxygen free radicals and conservation of energy metabolism are required. Protein kinases, transcription factors, and immediate early genes appear to transduce the signal into a tolerant response. Although the mechanism of ischemic tolerance remains uncertain, its discovery provides the focus for further understanding of the mechanism of endogenous neuroprotection and the potential of novel therapeutic strategies for neuroprotection. Such neuroprotective strategies may extend beyond ischemic tolerance to include other brain injury states as well.