Oxidative stress in hypothalamic neurons during experimental sepsis

• Grant number: 12/05489-5
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): August 01, 2012
• Effective date (End): June 30, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal researcher: Maria José Alves da Rocha
• Grantee: Fazal Wahab
• Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Despite considerable technological advances, systemic infections, including sepsis and its complications (septic shock and multiple organ dysfunctions) still are the major cause of death in Intensive Care Units all over the world. The incidence of these symptoms has increased in the last decade, not only because we still encounter a considerable lack of knowledge on sepsis, but also due to an increasing ageing in the population demography, an increase in the application of invasive surgical techniques, and an increase in the number of immunocompromised individuals. The morbidity and associated mortality rate of sepsis and its different clinical stages represent a major challenge to medical doctors, especially since current treatments are merely those of support. Important progress in the comprehension of the pathophysiology of sepsis has been made through experiments, but many more studies are still needed to come to a more profound understanding of the alterations caused by this disease. Sepsis induces excessive production and release of inflammatory mediators such as cytokines and nitric oxide (NO), which may directly or indirectly affect the central nervous system and induce autonomic and neuroendocrine alterations. Clinical and experimental studies report that the initial phase of sepsis is characterized by elevated plasma vasopressin concentrations. However in the late phase, thought the significant decrease in the arterial pressure, the vasopressin secretion decrease and the plasma concentrations remain inapropriately low, contributing to the hypotension, vasodilator shock and death. Some studies attribute this deficiency in hormone secretion to apoptosis in the hypothalamic nuclei. Considering the role of AVP in the vasopressor response, the elucidation of the mechanisms of the deficient hormone synthesis may contribute to therapy during sepsis. Our objective will be to investigate the hypothalamic neuronal apoptosis that could explain the impairment of vasopressin secretion during experimental sepsis.