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 these clinical 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 secretion occurs due to oxidative stress or apoptosis in the hypothalamic nuclei caused by the excessive NO (NO) production in the brain. This NO overproduction during experimental sepsis is related to the increased interleukin-1² (IL-1²) and the 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.
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