Photo of Domenico Tupone, PhD

Domenico Tupone PhD

  • 5036143771
    • Research Assistant Professor of Neurological Surgery, Division of Skull Base and Cerebrovascular School of Medicine

Hibernation is characterized by dramatic shifts in normal central nervous system (CNS) regulation of body temperature and normal sleep-wake state electroencephalogram (EEG) patterns.

Survival and recovery of function following ischemic injury (e.g., stroke) is significantly enhanced by the reduced metabolism and oxygen demands of ischemic tissue that result from lowering the temperature of ischemic tissue.

My research is focused on understanding (a) the intersection of CNS circuits regulating body temperature and sleep-wake state, (b) the CNS mechanisms responsible for alterations in thermoregulation and sleep-wake state during hibernation and torpor-like states, and (c) the application of this framework to the induction of therapeutic hypothermia, particularly related to improving outcomes in models of ischemic injury.

My research aims to test the hypothesis that a hibernation-like state can be replicated in non-hibernating mammals, and that the hypothermia and reduced cortical activity characteristic of the hibernating state will be therapeutically-effective in reducing tissue damage and loss of function following myocardial infarction, brain hemorrhage or brain ischemia. A greater understanding of the CNS systems regulating body temperature and sleep-wake state, and of the neuropharmacological underpinnings of hibernation is key to the development of pharmacological approaches to inducing a novel homeostatic state, featuring deep hypothermia and reduced cortical function that supports the maintenance and recovery of vital physiological functions. Comparing the regulation of body temperature, cardiovascular, metabolic, sleep and endocrine variables in normothermic and hypothermic homeostatic states will lead to a new vision of physiological regulation in deep hypothermia, which has the potential for enormous therapeutic relevance.

Currently I am pursuing studies on autonomic regulation (a) in the context of stroke pathologies, (b) to develop approaches for the induction of a deep hypothermia, and (c) to understand the basis for the thermally- and metabolically-shifted homeostasis of torpor-like states that might be inducible in non-hibernating mammals.

Overall, these studies on the CNS regulation of body temperature and metabolism, cardiovascular and cortical functions during normal, hypothermic and stroke conditions will indicate how these functions are dysregulated following stroke, and how we can ameliorate these dysfunctions. Additionally, an increased knowledge about autonomic regulation during deep hypothermia will suggest approaches to manage the induction, maintenance and recovery from deep hypothermia under normal and pathological conditions.

News Items of Interest 

2016 Italo-Americano, Domenico Tupone, PhD: Researching Therapeutic Hypothermia for Better Stroke Treatment by Kerry-Lynne Demarinis

2015 Mezz'ora al TG Canale 21, Ibernazione by Cristina Barone

2014 Digital Journal: Cryogenic success using rats by Tim Sandle

2013 Science News: Rats induced into hibernation-like state by Laura Senders

Education

  • Ph.D., Alma Mater Studiorum University of Bologna, Bologna Italy 2010
  • M.S., Alma Mater Studiorum University of Bologna, Bologna Italy 2006

Publications

  • "REM sleep and endothermy : Potential sites and mechanism of a reciprocal interference." Frontiers in Physiology  In: , Vol. 8, No. AUG, 624, 24.08.2017.
  • "Thermoregulatory inversion : A novel thermoregulatory paradigm." American Journal of Physiology - Regulatory Integrative and Comparative Physiology In: , Vol. 312, No. 5, 30.05.2017, p. R779-R786.
  • "Parabrachial complex links pain transmission to descending pain modulation." Pain In: , Vol. 157, No. 12, 10.08.2016, p. 2697-2708.
  • "Hibernation, hypothermia and a possible therapeutic "shifted homeostasis" induced by central activation of a1 adenosine receptor (A1AR)." Japanese Journal of Neuropsychopharmacology In: , Vol. 36, No. 2, 01.04.2016, p. 51-54.
  • "Hibernation, Hypothermia and a Possible Therapeutic "Shifted Homeostasis" Induced by Central Activation of A1 Adenosine Receptor (A1AR)." Japanese Journal of Psychopharmacology In: , Vol. 36, No. 2, 01.04.2016, p. 51-54.
  • "Enhanced slow-wave EEG activity and thermoregulatory impairment following the inhibition of the lateral hypothalamus in the rat." PLoS One  In: , Vol. 9, No. 11, e112849, 14.11.2014.
  • "Central neural regulation of brown adipose tissue thermogenesis and energy expenditure." Cell Metabolism  In: , Vol. 19, No. 5, 06.05.2014, p. 741-756.
  • "The direct cooling of the preoptic-hypothalamic area elicits the release of thyroid stimulating hormone during wakefulness but not during REM sleep." PLoS One  In: , Vol. 9, No. 2, e87793, 03.02.2014.
  • "Waking and sleeping in the rat made obese through a high-fat hypercaloric diet." Behavioural Brain Research  In: , Vol. 258, 01.01.2014, p. 145-152.
  • "Autonomic regulation of brown adipose tissue thermogenesis in health and disease : Potential clinical applications for altering BAT thermogenesis." Frontiers in Neuroscience In: , No. 8 FEB, 14, 2014.
  • "Highlights in basic autonomic neurosciences : Central adenosine A1 receptor - The key to a hypometabolic state and therapeutic hypothermia?" Autonomic Neuroscience: Basic and Clinical In: , Vol. 176, No. 1-2, 06.2013, p. 1-2.
  • "The inhibition of neurons in the central nervous pathways for thermoregulatory cold defense induces a suspended animation state in the rat." Journal of Neuroscience  In: , Vol. 33, No. 7, 13.02.2013, p. 2984-2993.
  • "α2 adrenergic receptor-mediated inhibition of thermogenesis." Journal of Neuroscience In: , Vol. 33, No. 5, 30.01.2013, p. 2017-2028.
  • "Central activation of the A1 adenosine receptor (A1AR) induces a hypothermic, torpor-like state in the rat." Journal of Neuroscience In: , Vol. 33, No. 36, 2013, p. 14512-14525.
  • "Waking and Sleeping following Water Deprivation in the Rat." PLoS One  In: , Vol. 7, No. 9, e46116, 24.09.2012.
  • "Central control of brown adipose tissue thermogenesis." Frontiers in Endocrinology  In: , Vol. 3, No. JAN, Article 5, 2012.
  • "Orexin modulates brown adipose tissue thermogenesis." Biomolecular Concepts In: , Vol. 3, No. 4, 2012, p. 381-386.
  • "An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis." Journal of Neuroscience In: , Vol. 31, No. 44, 02.11.2011, p. 15944-15955.
  • "Cutaneous vasodilation elicited by disinhibition of the caudal portion of the rostral ventromedial medulla of the free-behaving rat." Neuroscience In: , Vol. 165, No. 3, 03.02.2010, p. 984-995.

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