Contribution of central oxygen sensing mechanisms to the ventilatory responses to systemic hypoxia and cerebral hypoperfusion

• Grant number: 25/03278-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Daniel Breseghello Zoccal
• Grantee: Leticia Rodrigues Mendes
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 22/05717-0 - Analyzing breathing irregularities during the post-natal period in spontaneously hypertensive rats, AP.R

Abstract

The ventilatory response to hypoxia is mediated by peripheral chemoreceptors located in the carotid bodies, which detect reduced oxygen (O¿) availability in the blood and trigger a compensatory increase in pulmonary ventilation. However, if the arterial partial pressure of oxygen (PO¿) is not restored, a secondary respiratory depression occurs, attributed to central nervous system (CNS) suppression. Additionally, evidence suggests the presence of O¿-sensitive astrocytes in the CNS, which detect changes in parenchymal PO¿ and modulate ventilation independently of peripheral chemoreceptors. Despite these findings, no in vivo studies have directly correlated tissue PO¿ variations in the CNS with ventilatory adjustments under hypoxic conditions. Thus, this study will investigate the hypothesis that central O¿ chemoreceptors can stimulate the respiratory network and promote ventilatory responses to central hypoxia. To reach this goal, adult male Holtzman rats will be anesthetized with urethane (1.2 g/kg, i.v.) and instrumented to record physiological parameters such as PO¿ in the brainstem, peripheral O¿ saturation, cerebral blood flow, body and brain temperature, electromyographic activity of the diaphragm (DIA), abdominal (ABD), and genioglossus (GG) muscles, and systemic arterial pressure. Three experimental protocols will be applied while monitoring physiological parameters: (1) exposure to different levels of systemic hypoxia (12, 10, and 8% O¿ for 20 min); (2) repetition of the previous protocol in animals with carotid body denervation; and (3) infusion of a saline solution into the lateral ventricle to induce increased intracranial pressure and reduced cerebral blood flow. The results will provide insights into the central and peripheral determinants of the ventilatory response to hypoxia, contributing to a deeper understanding of the neural mechanisms regulating breathing under low O¿ availability. (AU)