Identification of cytokine receptors and Toll-like receptor 4 in the baroreceptor afferents of rats subjected to systemic inflammation

• Grant number: 21/03764-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2021
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Evelin Capellari Cárnio
• Grantee: Fernanda Brognara Penteado Dias
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Neuroimmune interactions have been extensively explored in order to find new therapeutic targets for inflammatory diseases. With the discovery of the "cholinergic anti-inflammatory pathway", several studies were conducted exploring the anti-inflammatory potential of the vagus nerve. However, more recently, evidence has suggested that baroreceptors (essential for arterial pressure control) may also have a role in modulating the immune system. Thus, the present study will investigate the presence of Toll-like receptor 4 and receptors for cytokines in baroreceptor afferents from rats. Therefore, about 5 to 7 days before the experiment, male Sprague-Dawley rats will receive the DiI marker from identifying the baroreceptor afferents. After this period, the animals will be anesthetized, and the arterial pressure and the aortic depressor nerve activity will be recorded, and body temperature will be monitored. Then, the aortic arch, the nodose ganglion, the aortic depressor nerve and blood samples will be collected at different times - before (baseline) and after (30, 60, 90 and 120 min) the administration of saline (control group) or LPS (experimental group). LPS administration will be used to induce systemic inflammation. Hemodynamic parameters, aortic depressor nerve activity and baroreflex sensitivity will be evaluated using specific software. The expression of cytokine receptors and Toll-like receptor 4 in the collected tissues will be analyzed using PCR, Western blot and immunofluorescence techniques at the different times studied. Plasma concentrations of cytokines, nitrate/nitrite and vasopressin, will be identified using specific methods to validate the model of systemic inflammation. The present study is expected to identify immune system receptors' presence in baroreceptor afferents, contributing to studies involving baroreceptors' participation in neuroimmune communication and suggesting a new therapeutic target for the immune system modulation. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CESARINO, LUIZ G.; BROGNARA, FERNANDA; CASTANIA, JACI A.; SALGADO, HELIO C.. Baroreflex Activation Contributes to the Progression of the Systemic Inflammatory Response in Unanesthetized Rats. FASEB JOURNAL, v. 36, p. 1-pg., 2022-01-01. (20/06043-7, 20/08312-5, 21/03764-8)

BROGNARA, FERNANDA; CASTANIA, JACI; DIAS, DANIEL; SALGADO, HELIO; PATON, JULIAN; CARNIO, EVELIN. Aortic baroreceptor afferent activity during systemic inflammation. PHYSIOLOGY, v. 38, p. 2-pg., 2023-05-01. (21/05554-0, 21/03764-8)