Ischemic preconditioning in the brain

Brain ischemia is responsible for significant morbidity and mortality associated with cardiovascular surgery, and is the end result of multiple disease states, including cardiac arrest, stroke, and traumatic brain injury. Despite significant resources dedicated to developing neuroprotective strategies, little progress has been made in this regard. Neuronal ischemic preconditioning is an endogenous neuroprotective strategy that provides sustained and robust ischemic tolerance. Identification of the mechanisms responsible for mediating the preconditioning response may offer novel therapeutic targets and further our understanding of the natural adaptations to brain injury.

Recent research efforts have elucidated many intracellular signaling pathways that ultimately lead to ischemic tolerance after a preconditioning stimulus. Most of these are associated with glutamate receptor signal transduction, the intracellular kinases, and several transcription regulators. Microarray analysis has identified several gene families that warrant further investigation to identify novel candidates for neuroprotective therapies. These include genes involved in synaptic architecture and signal propagation, cell cycle and transcription regulators, and mediators of apoptosis such as the heat shock proteins and anti-apoptotic mitochondrial proteins.

Neuronal ischemic preconditioning is an endogenous mechanism that leads to robust neuroprotection from ischemia. Identification of the upstream pathways that initiate preconditioning and candidate genes that mediate this phenomenon may offer novel therapeutic targets, with applicability to a variety of disease states and perioperative complications.