Sleep deprivation disrupts vital biological processes that are necessary for cognitive ability and physical health, but the physiological changes that underlie these outward effects are largely unknown. The purpose of the present studies in the laboratory rat is to prolong sleep deprivation to delineate the pathophysiology and to determine its mediation. In the rat, the course of prolonged sleep deprivation has a syndromic nature and eventuates in a life-threatening state. An early and central symptom of sleep deprivation is a progressive increase in peripheral energy expenditure to nearly double normal levels. An attempt to alleviate this negative energy balance by feeding rats a balanced diet that is high in its efficiency of utilization prolongs survival and attenuates or delays development of malnutrition-like symptoms, indicating that several symptoms can be manipulated to some extent by energy and nutrient consumption. Most changes in neuroendocrine parameters appear to be responses to metabolic demands, such as increased plasma catecholamines indicating sympathetic activation. Plasma total thyroid hormones, however, decline to severely low levels; a metabolic complication that is associated with other sleep deprivation-induced symptoms, such as a decline in body temperature to hypothermic levels despite increased energy expenditure. Metabolic mapping of the brain revealed a dissociation between the energy metabolism of the brain and that of the body. Sleep deprivation's effects on cerebral structures are heterogenous and unidirectional toward decreased functional activity. The hypometabolic brain structures are concentrated in the hypothalamus, thalamus and limbic system, whereas few regions in the rest of the brain and none in the medulla, are affected. Correspondence can be found between some of the affected cerebral structures and several of the peripheral symptoms, such as hyperphagia and possible heat retention problems. The factor predisposing to mortality is a decreased resistance to infection. Lethal opportunistic organisms are permitted to infect the bloodstream, which presumably results in a cascade of toxic-like reactions. Host defense is thus the first system to fail. There is neither fever nor marked tissue inflammatory reactions typical of infectious disease states, suggesting that sleep deprivation is immunosuppressive. Each of the four major abnormalities identified-(1) a deep negative energy balance and associated malnutrition; (2) heterogeneous decreases in cerebral function; (3) low thyroid hormone concentrations; and (4) decreased resistance to infection-can be viewed as having an early origin during the sleep deprivation process to signify the foremost pathogenic situation to which the other abnormalities might be secondarily related. The findings therefore remain somewhat equivocal for a unitary function for sleep, but can support putative roles for sleep in thermoregulation, energy conservation, immune system integrity and tissue restoration.
