| Grant number: | 20/09399-7 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | September 01, 2020 |
| End date: | August 31, 2025 |
| Field of knowledge: | Biological Sciences - Physiology - Physiology of Organs and Systems |
| Principal Investigator: | Alexandre Alarcon Steiner |
| Grantee: | Eduardo Hermogenes Moretti |
| Host Institution: | Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 18/03418-0 - Hypothermia in Sepsis: causes and consequences, AP.TEM |
| Associated scholarship(s): | 23/14912-3 - ORGAN-SPECIFICITY OF METABOLIC REPROGRAMMING AND EXTRACELLULAR VESICLE-BASED COMMUNICATION IN RESIDENT MACROPHAGES, BE.EP.PD |
Abstract A change in body temperature is a hallmark of systemic inflammation. Although fever (rise in body temperature) is the most prevalent and studied response, hypothermia (decrease in body temperature) occurs in the most severe cases. Recent studies indicate that hypothermia does not result from thermoregulatory failure. On the contrary, it appears to be a regulated response with biological value when the costs of fever exceed its benefits. However, the mechanisms that govern the shift from fever to hypothermia remain unclear. Here, we will test the hypothesis that a slight drop in regional blood flow and, consequently, brain oxygenation is the trigger for brain-driven reductions in metabolic rate and body temperature. This hypothesis will be tested in rats pre-implanted with sensors for PO2, blood flow and brown adipose tissue temperature, in addition to electrodes for recording sympathetic activity. Systemic inflammation will be induced by moderate and high doses of LPS at an ambient temperature that is suitable for the development of hypothermia. If the hypothesis is correct, the hypothermic response is expected to be preceded by a drop in brain perfusion and oxygenation. Likewise, the drop in brain oxygenation should precede the inhibition of the sympathetic nerves that innervate the brown adipose tissue. Granger's causality tests will be used to statistically evaluate the temporal relationship between these variables. In subsequent experiments, we will assess whether the manipulation of brain oxygenation can impact the development of LPS-induced hypothermia. Brain oxygenation will be manipulated using strategies that increase global oxygenation (erythropoietin, hypoxia acclimation and perfluoroalkanes), in combination with partial occlusion of the carotid arteries. | |
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