Differences and similarities in neuroprotective molecu lar pathways ac t ivated by d is t inc t preconditioning inducers

The identification of neuroprotective therapies is gaining great interest in the design of strategies to prevent neuronal death. However, up until now all tested approaches have been unsuccessful despite many years of clinical trials, mainly because of the numerous side effects observed in humans and absent in animals used at the preclinical level. The neuroprotective strategy known as brain preconditioning is becoming important with the increased understanding of the endogenous mechanisms able to induce tolerance. Over the years, several stimuli have been described as possible preconditioning inducers, and many molecular pathways have been proposed as plausible mechanisms to explain the neuroprotection. The nature of these mechanisms is strongly influenced by the temporal profile examined and the nature of the stimulus able to induce conditioning protection. The purpose of the present review is to summarize the most studied molecular mechanisms involved in the different kinds of conditioning, highlighting differences and similarities. Knowledge of these mechanisms may bring to light those molecular pathways that must be activated or inhibited in order to protect the brain. This review describes the possible differences and similarities among neuroprotective pathways involved in four different types of preconditioning stimuli: pharmacological, physical, surgical and thermoregulatory.