Sleep, Preconditioning and Stroke

Sleep is a complex physiological and behavioral state, which is needed for homeostasis at a cellular (neurons), organ (brain), and individual level, known to be fundamental for survival. Despite its importance, it is estimated that one third of the adult population is sleep deprived1 or complains about sleep disturbances.2 Sleep disorders, classified into 6 major categories according to the recent International Classification of Sleep Disorders,3 determine sleep fragmentation, which in turn induces autonomic nervous system dysfunction, increases inflammation, alters coagulation, and induces oxidative stress responses.4,5 Sleep deprivation (SD)/fragmentation has been linked to several pathological conditions, including stroke (in the present review, the term stroke always refers to ischemic stroke).6,7 In the first part of this review, we address the role of sleep modulation in the pathophysiology of brain ischemia (Figure 1),8–12 and we briefly discuss the current epidemiological evidence linking sleep disorders to stroke risk. In the second part, we review the concept of ischemic preconditioning (IP), and we discuss the role of sleep as a potential preconditioning factor able to induce ischemic tolerance and neuroprotection.13 Figure 1. The vicious and virtuous circles of sleep and stroke interaction. Sleep disruption after experimental stroke is detrimental, whereas promoting sleep after an ischemic event facilitates neuroplasticity and recovery in turn determining a better stroke outcome. REM indicates rapid eye movement; and SWS, slow-wave sleep. ### Animal Studies Sleep may be artificially manipulated by inducing either SD or sleep enhancement before or after experimental stroke. Animal models have shown that increasing the length and repetition of SD after stroke is linked to detrimental effects affecting both stroke evolution and functional recovery.9,11,14 Additionally, it has been shown that the number of apoptotic …