Heat acclimation: a unique model of physiologically mediated global preconditioning against traumatic brain injury

Sub-lethal exposure to practically any harmful stimulus has been shown to induce consequent protection against more severe stress. This preconditioning (PC) effect may be achieved by exposure to different stressors, indicating that the induction of tolerance involves activation of common protective pathways. Chronic exposure to moderate heat (heat acclimation, HA) is a unique PC model, since this global physiological adaptation, as opposed to discrete organ PC, has been shown to induce cross-tolerance against other stressors, including closed head injury (CHI). HA animals show accelerated functional recovery after injury which is accompanied by reduced secondary brain damage. However, the precise mechanisms underlying this phenomenon have not been thoroughly studied until recently. Here we will address the concept of PC, highlighting the unique properties of HA as a model which can be used for the study of endogenous protective pathways triggered by PC procedures. Several molecular mechanisms which are suggested to mediate HA-induced neuroprotection will also be discussed, bringing to light their potential contribution to the development of traumatic brain injury treatment strategies utilizing therapeutic augmentation of endogenous defense mechanisms.