Possible Human Endogenous Cryogens

Shido, Osamu; Sugimoto, Naotoshi

doi:10.2174/138920311795906682

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…By rejecting the hypothesis that LPS-induced hypothermia is triggered by a fall in brain oxygenation, the results of the present study favor the alternate hypothesis of hypothermia being triggered by the direct action of inflammatory mediators on the brain (17–19). This prompted us to investigate the dynamics of the cytokine responses in relation to the dynamics of the T c responses.…”

Section: Resultscontrasting

confidence: 67%

Interplay between brain oxygenation and the development of hypothermia in endotoxic shock

Moretti,

Lino,

Steiner

2024

Shock

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There is evidence to suggest that the hypothermia observed in the most severe cases of systemic inflammation or sepsis is a regulated response with potential adaptive value, but the mechanisms involved are poorly understood. Here, we investigated the interplay between brain oxygenation (assessed by tissue PO2) and the development of hypothermia in unanesthetized rats challenged with a hypotension-inducing dose of bacterial lipopolysaccharide (LPS, 1 mg/kg i.v.). At an ambient temperature of 22 °C, oxygen consumption (V̇O2) began to fall only a few minutes after the LPS injection, and this suppression in metabolic rate preceded the decrease in core temperature. No reduction in brain PO2 was observed prior to the development of the hypometabolic, hypothermic response, ruling out the possibility that brain hypoxia served as a trigger for hypothermia in this model. Brain PO2 was even increased. Such an improvement in brain oxygenation could reflect either an increased O2 delivery or a decreased O2 consumption. The former explanation seems unlikely because blood flow (cardiac output) was being progressively decreased during the recording period. On the other hand, the decrease in V̇O2 usually preceded the rise in PO2, and an inverse correlation between V̇O2 and brain PO2 was consistently observed. These findings do not support the existence of a closed-loop feedback relationship between brain oxygenation and hypothermia in systemic inflammation. The data are consistent with a feedforward mechanism in which hypothermia is triggered (possibly by cryogenic inflammatory mediators) in anticipation of changes in brain oxygenation to prevent the development of tissue hypoxia.

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Section: Resultscontrasting

confidence: 67%

Interplay between brain oxygenation and the development of hypothermia in endotoxic shock

Moretti,

Lino,

Steiner

2024

Shock

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“…Anapyrexia-inducing agents could be used alone or as an adjunct therapy to forced cooling. As we search for clinically viable agents for induction of anapyrexia (124,314), gaseous mediators and related drugs pose as candidates that cannot be ignored.…”

Section: Anapyrexiamentioning

confidence: 99%

Gaseous Mediators in Temperature Regulation

Branco

Soriano

Steiner

2014

Comprehensive Physiology

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Deep body temperature (Tb) is kept relatively constant despite a wide range of ambient temperature variation. Nevertheless, in particular situations it is beneficial to decrease or to increase Tb in a regulated manner. Under hypoxia for instance a regulated drop in Tb (anapyrexia) is key to reduce oxygen demand of tissues when oxygen availability is diminished, leading to an increased survival rate in a number of species when experiencing low levels of inspired oxygen. On the other hand, a regulated rise in Tb (fever) assists the healing process. These regulated changes in Tb are mediated by the brain, where afferent signals converge and the most important regions for the control of Tb are found. The brain (particularly some hypothalamic structures located in the preoptic area) modulates efferent activities that cause changes in heat production (modulating brown adipose tissue activity and perfusion, for instance) and heat loss (modulating tail skin vasculature blood flow, for instance). This review highlights key advances about the role of the gaseous neuromodulators nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) in thermoregulation, acting both on the brain and the periphery.

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“…Severe systemic inflammation has been shown to cause hypotension and hypothermia as a protective response to the detrimental effects of inflammation, as observed following robust fever (Garami et al, 2018; Kluger et al, 1998; Leon et al, 1998). Several CNS signaling molecules are considered cryogenic (e.g., TNF‐alpha, glucocorticoids, taurine, GABA), meaning they endogenously combat the pyrogenic fever response to inflammation (Frosini et al, 2000; Shido & Sugimoto, 2011). Additionally, cryogenic signaling has been shown to act during periods of hypoxia/ischemia to reduce the metabolic rate in local tissues (Frosini et al, 2000; Leon, 2004; Shido & Sugimoto, 2011).…”

Section: Focal Versus Systemic Th Treatment: a Brief Mechanistic Comparisonmentioning

confidence: 99%

“…Several CNS signaling molecules are considered cryogenic (e.g., TNF‐alpha, glucocorticoids, taurine, GABA), meaning they endogenously combat the pyrogenic fever response to inflammation (Frosini et al, 2000; Shido & Sugimoto, 2011). Additionally, cryogenic signaling has been shown to act during periods of hypoxia/ischemia to reduce the metabolic rate in local tissues (Frosini et al, 2000; Leon, 2004; Shido & Sugimoto, 2011). After stroke, TH modulates levels of numerous different cryogenic signaling molecules, some of which are known to exert both protective and injurious actions in a dose and region‐dependent manner (Ceulemans et al, 2010; Menzie et al, 2013; Wisnowski et al, 2016).…”

Section: Focal Versus Systemic Th Treatment: a Brief Mechanistic Comparisonmentioning

confidence: 99%

Targeting focal ischemic and hemorrhagic stroke neuroprotection: Current prospects for local hypothermia

Liddle

Kalisvaart

Abrahart

et al. 2021

Journal of Neurochemistry

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Therapeutic hypothermia (TH) has applications dating back millennia. In modern history, however, TH saw its importation into medical practice where investigations have demonstrated that TH is efficacious in ischemic insults, notably cardiac arrest and hypoxic‐ischemic encephalopathy. As well, studies have been undertaken to investigate whether TH can provide benefit in focal stroke (i.e., focal ischemia and intracerebral hemorrhage). However, clinical studies have encountered various challenges with induction and maintenance of post‐stroke TH. Most clinical studies have attempted to use body‐wide cooling protocols, commonly hindered by side effects that can worsen post‐stroke outcomes. Some of the complications and difficulties with systemic TH can be circumvented by using local hypothermia (LH) methods. Additional advantages include the potential for lower target temperatures to be achieved and faster TH induction rates with LH. This systematic review summarizes the body of clinical and preclinical LH focal stroke studies and raises key points to consider for future LH research. We conclude with an overview of LH neuroprotective mechanisms and a comparison of LH mechanisms with those observed with systemic TH. Overall, whereas many LH studies have been conducted preclinically in the context of focal ischemia, insufficient work has been done in intracerebral hemorrhage. Furthermore, key translational studies have yet to be done in either stroke subtype (e.g., varied models and time‐to‐treat, studies considering aged animals or animals with co‐morbidities). Few clinical LH investigations have been performed and the optimal LH parameters to achieve neuroprotection are unknown.

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Possible Human Endogenous Cryogens

Cited by 6 publications

References 33 publications

Interplay between brain oxygenation and the development of hypothermia in endotoxic shock

Interplay between brain oxygenation and the development of hypothermia in endotoxic shock

Gaseous Mediators in Temperature Regulation

Targeting focal ischemic and hemorrhagic stroke neuroprotection: Current prospects for local hypothermia

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