Cerebral conditioning: Mechanisms and potential clinical implications

Cerebral conditioning is defined as the mild harmful stimuli applied to the brain before ischemia (preconditioning), during ischemia (perconditioning), immediately, a few hours or days after reperfusion (postconditioning). Various noxious stimuli can precondition, percondition or postcondition the brain, including ischemia, hypoxia or anesthetics to induce tolerance to lethal ischemia/reperfusion injury. The mechanisms underlying cerebral conditioning range from sensors and transducers including extracellular neurotransmitters and receptors, intracellular signals, transcription factors and epigenetic regulation, to effectors involving physiological protection, stem cells, heat shock proteins, Bcl-2, mitochondria, ubiquitin - proteasome pathway and autophagy pathway. Based on the large number of studies conducted in animal models, researchers explore the clinical application of cerebral conditioning. Remote ischemic conditioning is considered the most applicable and clinically relevant form of cerebral conditioning. The translational research also involves development of the biomarkers of conditioning and optimization of organ transplantation. The present review summarized the recent progress in signaling pathways and clinical applications of cerebral conditioning to explore the possibility to develop a potential therapeutic strategy for the prevention and treatment of ischemic stroke.