STUDY OF THE INFLAMMATORY PROCESS AND INTESTINAL FUNCTION AFTER BRAIN DEATH IN RATS: SEX DIFFERENCES AND TREATMENT WITH 17¿-ESTRADIOL

• Grant number: 25/00587-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Cristiano de Jesus Correia
• Grantee: Cristiano de Jesus Correia
• 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
• City of the host institution: São Paulo
• Associated researchers: Ana Cristina Breithaupt Faloppa ; Luiz Felipe Pinho Moreira

Abstract

Intestinal transplantation, is a relatively new practice in the field of organ transplantation in comparison with other organs, is the most effective life-saving therapy for patients with life-threatening complications of irreversible intestinal failure and underlying gastrointestinal disease. However, despite significant advances in the last decades, intestinal transplantation remains a challenging procedure. Furthermore, it is the least frequent type of transplant due to several factors, such as frequent rejection, post-transplant infections and ischemia-reperfusion injury (IRI).In parallel, clinical studies evidences the differences in short- and long-term prognosis in transplants of different organs due to the sex of the donor. Studies clinical and experimental shows the brain death impact on the viability of the organ to be transplanted and highlights the importance of the donor's condition in the final transplant results. Brain death triggers activation of the immune system, characterized by increased expression of inflammatory mediators, including cytokines, chemokines, and adhesion molecules, and by inflammatory cell infiltration represented by the presence of macrophages, polymorphonuclear leukocytes, and T lymphocytes in the heart, lung, kidney, and intestine. Although there is evidence that the immune response (innate and adaptive) differs between men and women, sexual dimorphism does not receive enough attention as a potential factor for understanding the different immune responses observed between men and women.Sex hormones can exert modulating activity on the inflammatory response. Studies indicate that estradiol improves intestinal barrier function by increasing the expression of proteins related to cell junctions and reducing intestinal permeability, which helps maintain intestinal integrity in a model of ischemia and reperfusion. Acute reductions in the concentration of female sex hormones can cause changes in several systems, including the immune system. The consequent acute reduction in female sex hormone levels after brain death would result in an increase in the inflammatory response generated, and female sex hormones, as modulators of the immune response, can be considered potential modulators of the events triggered by BD. Based on the idea that sexual dimorphism exists in the immune system's response to brain death and that estradiol could act by modulating the intestinal and systemic inflammatory response, the study plan presented here proposes to study the differences between the sexes in intestinal function and motility and to investigate the effect of estradiol treatment in a brain death model in rats. (AU)