The role of estradiol in the maintenance of brain-dead organ donors: from pathophysiology to treatment

Organ transplantation is considered the ideal treatment for some diseases, such as terminal heart failure. Clinical and experimental evidence emphasizes the impact of brain death (BD) on the viability of the organ to be transplanted and highlights the importance of the donor's status in the final results of the transplant. BD affects organ function through several mechanisms, including hemodynamic changes, hormonal changes, and systemic inflammation resulting from the activation of the immune system, characterized by increased release/synthesis of inflammatory mediators, expression of adhesion molecules, and by inflammatory cell infiltrate. Studies confirm the donor's sex as one of the factors that influence the success of organ transplantation and show a worse prognosis in heart transplantation with grafts from women. Female sex hormones participate in modulating the magnitude of the inflammatory response and acute reductions in the concentration of female sex hormones can cause changes in several systems, including the immune system. Importantly, estradiol protects the cardiovascular system against ischemic, inflammatory, and metabolic injuries. Preliminary data indicate an acute reduction in estrogen concentrations and exacerbation of the pulmonary inflammatory process in females after BD. In this context, this thesis aims to describe the effects of female sex hormone modulation on systemic inflammation and organ damage in brain-dead donors. Differences in microcirculatory changes caused by BD and inflammatory mediators between sexes were analyzed. Considering female sex hormones as immunomodulators and the association between severe organ inflammation in female animals after BD with acute estradiol reduction, we investigated the potential therapeutic effects of treatment with 17β-estradiol to mitigate the deleterious process in the heart, lung, and kidney of rats with BD.