title: Induction of therapeutic hypothermia by pharmacological modulation of temperature-sensitive TRP channels: theoretical framework and practical considerations.
abstract: Therapeutic hypothermia has emerged as a remarkably effective method of neuroprotection from ischemia and is being increasingly used in clinics. Accordingly, it is also a subject of considerable attention from a basic scientific research perspective. One of the fundamental problems, with which current studies are concerned, is the optimal method of inducing hypothermia. This review seeks to provide a broad theoretical framework for approaching this problem, and to discuss how a novel promising strategy of pharmacological modulation of the thermosensitive ion channels fits into this framework. Various physical, anatomical, physiological and molecular aspects of thermoregulation, which provide the foundation for this text, have been comprehensively reviewed and will not be discussed exhaustively here. Instead, the first part of the current review, which may be helpful for a broader readership outside of thermoregulation research, will build on this existing knowledge to outline possible opportunities and research directions aimed at controlling body temperature. The second part, aimed at a more specialist audience, will highlight the conceptual advantages and practical limitations of novel molecular agents targeting thermosensitive Transient Receptor Potential (TRP) channels in achieving this goal. Two particularly promising members of this channel family, namely TRP melastatin 8 (TRPM8) and TRP vanilloid 1 (TRPV1), will be discussed in greater detail.
authors.affiliation: Department of Molecular Physiology and Biophysics Graduate Program; Cardiovascular Sciences Track; Baylor College of Medicine , Houston, TX, USA.
authors.forename: Viktor V
authors.initials: VV
authors.lastname: Feketa
authors.affiliation: Department of Molecular Physiology and Biophysics Graduate Program; Cardiovascular Sciences Track; Baylor College of Medicine, Houston, TX, USA; Department of Anesthesiology; Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Marrelli
keywords: DMH, dorso-medial hypothalamus; MPA, medial preoptic area of hypothalamus; TRP, Transient Receptor Potential; TRPA1, Transient Receptor Potential cation channel, subfamily A, member 1; TRPM8, Transient Receptor Potential cation channel, subfamily M, member 8; TRPV1, Transient Receptor Potential cation channel, subfamily V, member 1; TRPV2, Transient Receptor Potential cation channel, subfamily V, member 2; TRPV3, Transient Receptor Potential cation channel, subfamily V, member 3; TRPV4, Transient Receptor Potential cation channel, subfamily V, member 4; ThermoTRPs; ThermoTRPs, Thermosensitive Transient Receptor Potential cation channels; body temperature; core temperature; pharmacological hypothermia; physical cooling; rMR, rostral medullary raphe region; therapeutic hypothermia; thermopharmacology; thermoregulation; thermosensitive ion channels