Evaluation of the estradiol treatment on pulmonary inflammaton on female rats subject to brain death

• Grant number: 16/03692-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2018
• Effective date (End): July 31, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Cristina Breithaupt Faloppa
• Grantee: Fernanda Yamamoto Ricardo da Silva
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 18/07289-0 - Evaluation of estradiol effects on lung of brain dead female rats after ex vivo perfusion, BE.EP.DR

Abstract

Organ transplantation from Brain Dead (BD) individuals is the possible treatment for many pulmonary advanced diseases and could improve the life quality and extend survival. Clinical and experimental studies evidenced the BD impact on transplanted organ viability. Also the lung is one the most affected organs by BD, which is associated with hemodynamic instability and inflammatory and immunologic alterations. Important hormonal and metabolic changes occur after hypothalamic/pituitary failure in experimental models of brain death, which are associated with events before brain death, such as trauma and hemorrhage, adding to the final inflammatory result of the organ donor. Studies highlight the greater risk in lung transplants from women donors to male recipients. On the other hand lung transplant between women show better results. Previous results from our group indicated in female rats a more relevant pulmonary inflammation, combined with acute reduction of female sex hormones. These findings, together with clinical and experimental studies reinforcingl the estradiol protector effect on immune system, pulmonary inflammation and proinflammatory mediators release, reinforce the significance of assessing estradiol treatment effects on pulmonary inflammatory response in female rats submitted to brain death and also the evaluation of estradiol as a therapeutic alternative to mitigate the deleterious effects of BD. Thus in this project we aim to investigate the estradiol treatment effect on lung inflammation after brain death in female rats. We intend to evaluate: (1) leukocyte mobilization to lung tissue, from the bone marrow and blood compartment after brain death; (2) lung microcirculation by intravital microscopy; (3) lung function by spirometry and gas exchange; (4) systemic and local release of inflammatory mediators; (5) protein expression of adhesion endothelial molecules on lung tissue; (6) in vitro leukocyte chemotaxis. (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)

FERNANDA YAMAMOTO RICARDO-DA-SILVA; ROBERTO ARMSTRONG-JR; MARINA VIDAL-DOS-SANTOS; CRISTIANO DE JESUS CORREIA; RAPHAEL DOS SANTOS COUTINHO E SILVA; LUCAS FERREIRA DA ANUNCIAÇÃO; LUIZ FELIPE PINHO MOREIRA; HENRI GERRIT DERK LEUVENINK; ANA CRISTINA BREITHAUPT-FALOPPA. Long–term lung inflammation is reduced by estradiol treatment in brain dead female rats. Clinics, v. 76, 2021-08-16. (16/03692-9, 17/11798-4, 18/07289-0)

RICARDO-DA-SILVA, FERNANDA YAMAMOTO; ARMSTRONG JR, ROBERTO; VIDAL-DOS-SANTOS, MARINA; CORREIA, CRISTIANO DE JESUS; COUTINHO E SILVA, RAPHAEL DOS SANTOS; DA ANUNCIACAO, LUCAS FERREIRA; PINHO MOREIRA, LUIZ FELIPE; DERK LEUVENINK, HENDRIK GERRIT; BREITHAUPT-FALOPPA, ANA CRISTINA. 17 beta-Estradiol Treatment Protects Lungs Against Brain Death Effects in Female Rat Donor. TRANSPLANTATION, v. 105, n. 4, p. 775-784, APR 2021. (17/11798-4, 18/07289-0, 16/03692-9)

RICARDO-DA-SILVA, FERNANDA YAMAMOTO; ARMSTRONG-JR, ROBERTO; VIDAL-DOS-SANTOS, MARINA; CORREIA, CRISTIANO DE JESUS; SILVA, RAPHAEL DOS SANTOS COUTINHO E; ANUNCIACAO, LUCAS FERREIRA DA; MOREIRA, LUIZ FELIPE PINHO; LEUVENINK, HENRI GERRIT DERK; BREITHAUPT-FALOPPA, ANA CRISTINA. Long-term lung inflammation is reduced by estradiol treatment in brain dead female rats. Clinics, v. 76, 2021. (16/03692-9, 17/11798-4, 18/07289-0)