Neurocognitive evaluation in sepsis survivors rats treated with simvastatin

• Grant number: 16/12561-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2016
• Effective date (End): July 31, 2017
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Maria José Alves da Rocha
• Grantee: Jéssica Priscila de Mélo
• Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Despite technological advances, sepsis and its consequence severe sepsis and septic shock are still the leading cause of death in Intensive Care Unit (ICU). The majority of the survivors of theseclinical conditions will present some cognitive impairment soon after discharge which can be or not over the years. Clinical and experimental studies, report that the initial phase of sepsis is characterized by high plasma levels of arginine vasopressin (AVP) and the late phase, by low levels, which contribute to hypotension, shock and death. Some studies show that the decreased AVP secretionoccurs due to oxidative stress or apoptosis in the hypothalamic nucleicaused by the excessive NO (NO) production in the brain. This NO overproduction during experimental sepsis is related to theincreased interleukin-1² (IL-1²) andthe inducible NO synthase (iNOS) in the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei that synthetize AVP. The increase in NO production in the brain especially after activation of iNOS, may alter mitochondrial bioenergetics and cause neuronal apoptosis in cognitive-related structures such as hypothalamus. Therefore is important to look for drugs to protect the brain against this mitochondrial bionergetic alteration. Since statins present several pleitrópicos effects including anti-inflammatory and anti-oxidant our hypothesis is that simvastatin may reduce cognitive dysfunction in sepsis survival rats by acting as a neuroprotective agent.