Brain temperature: from physiology and pharmacology to neuropathology

Brain temperature is a physiologic parameter that depends on metabolism-related intracerebral heat production and heat loss by cerebral circulation to the rest of the body and then to the external environment. Despite the importance of temperature as a metabolism-related parameter and a factor affecting neural activity and function, it is generally believed that brain temperature is a tightly regulated and highly stable homeostatic parameter. To challenge this view, we present data on fluctuations in brain temperature occurring in rats following exposure to various arousing stimuli and during different behaviors and discuss their mechanisms. Since most psychoactive drugs affect brain metabolism and vascular tone, thereby altering heat production and heat loss, we consider changes in brain temperature induced by several types of psychoactive drugs. Our focus here is on several widely used drugs of abuse (i.e., cocaine, heroin, methylenedioxymethamphetamine (MDMA)), which are used by humans at widely varying doses and often under conditions of psychophysiologic activation and in environments limiting natural heat loss. In contrast to physiologic brain hyperthermia that has a clear adaptive significance, drug-induced hyperthermia can reach pathologic levels, resulting in irreversible damage of brain cells, profound leakage of the blood-brain barrier, and multiple functional perturbations that can, in certain instances, be incompatible with life. We also discuss the complexities of considering brain temperature within the frameworks of physiologic regulation and homeostasis. While different adaptive mechanisms could, within some limits, compensate for an altered heat balance of the brain, real-life challenges often create situations where this balance cannot be adequately compensated for, resulting in acute life-threatening health complications and chronic neuropathology.