Thermoregulation: from basic neuroscience to clinical neurology. 1

The importance of problems associated with thermoregulation has been increasing. During recent decades, several major heatwaves have hit various regions of the planet, resulting in thousands of deaths due to heatstroke, and scientists have established that the threat to human life due to excessive heat associated with human activities is now unavoidable. During the same time period, mild hypothermia has been discovered as a life-saving treatment for several conditions, most notably those accompanied by brain hypoxia. Simultaneously, many things have changed in our understanding of the physiology and neuroscience of body temperature regulation. It has been established that brown adipose tissue is a thermoregulatory effector in humans – not only during the perinatal period (as thought previously), but also in adulthood. Several transient receptor potential channels have been discovered, many of which possess high sensitivity to temperature and may represent the molecular basis of thermoreception. Enormous progress has been achieved in the identification and characterization of the neural pathways of physiologic thermoeffectors, at least in rodents, and studies in humans have been initiated. A new, consensus concept has been firmly established: it is now believed that body temperature is regulated not by a unified system with a central integrator, comparator, and coordinator but by a federation of independent thermoeffector loops, which coordinate their activities via their common regulated variable – body temperature. To update neurologists, neuroscientists, trainees, and others on the current knowledge about thermoregulation, we have drawn on the experience and expertise of established leaders in the fields of thermoregulation and neurologic diseases and, collectively, prepared the two parts of this volume of the Handbook of Clinical Neurology. Part 1 (28 chapters) describes the elements of the thermoregulation system (receptors, effectors, and pathways) and explains how the system works and interacts with other homeostatic systems. Part 2 (26 chapters) deals with the clinical significance of body temperature, common conditions in which deep or peripheral body temperatures are changed, and thermoregulatory alterations present in several neurologic diseases, as well as with therapeutic hypo- and hyperthermia and antipyretic therapy. While working on this project, all authors have made an effort to follow the current consensusmodel of thermoregulation and to avoid referring to the outdated unified control system with its nonexistent complex circuits. The authors also avoided using engineering terms such as the reference signal (set point) or coordinator, as they are now more misleading than informative. We hope our effort will help neurologists to focus their search for the anatomic and physiologic substrates of thermoregulatory symptoms of neurologic diseases on the existing active and passive elements of the thermoregulation system. As the associate volume editors and the volume editor, we sincerely thank all the contributors to this volume for the indispensable roles they have played in bringing this endeavor to fruition.We believe that readers will find this volume to be a valuable contribution to the existing literature on thermoregulation.We hope that the volume will serve not only as a reference source for academic and practicing neurologists, but also as an educational resource for trainees in neurology and neuroscience, as well as for internists, intensivists, anesthesiologists, toxicologists, and all physicians and scientists interested in learning about thermoregulation. May our readers glean much from the collective knowledge and expertise shared with them on these pages. Andras Garami Luca Imeri Christopher J. Madden Alexandre A. Steiner Andrej A. Romanovsky