Regulation of gene expression in ischemic preconditioning in the brain

Stroke is the third leading cause of death and the leading cause of long-term disability, with very few effective treatments and limited progress in the effort to search for novel therapeutic approaches. The phenomenon that a sublethal ischemic insult induces protection against a subsequent severe ischemia, termed ischemic preconditioning (IPC), represents an endogenous protective approach against ischemic brain injury, and may direct a breakthrough to future therapeutic strategies. It is broadly accepted that new protein synthesis is required for IPC-mediated long-term neuroprotection; however, their relative regulatory mechanisms are poorly understood. In the present review, we summarize genomic-based studies on alterations in gene expression and protein synthesis, particularly categorizing potential pathways regulated by IPC. We also review the role of epigenetics, an inheritable genetic regulatory mechanism without changes in DNA sequence, in IPC-mediated neuroprotection.