Analysis of the neuroprotective effect of simvastatin on inflammatory and degenerative processes in cognitive brain areas of sepsis-surviving animals

• Grant number: 18/02295-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2018
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria José Alves da Rocha
• Grantee: Bruna Barissa Rossignolli
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Peripheral inflammatory mediators that reach the Central Nervous System (CNS) trigger the activation of microglial cells resulting in neuroinflammation. This inflammatory response may cause changes in the permeability of the blood-brain barrier (BBB), which with other alterations may lead to brain dysfunction causing the appearance of long-term neurological sequelae. Studies have shown that neurodegeneration is causes of several neurological diseases and that they would be associated with inflammatory processes. Cognitive dysfunctions and permanent memory deficits are neurological abnormalities commonly found in Alzheimer's disease (AD) and sepsis-associated encephalopathy (SAE). Damage to the hippocampus and cortex of patients with SAE results in reduced learning and memory. To minimize the development of cognitive dysfunctions and dementias in patients with SAE, the use of statins as a prior and continuous treatment has been proposed. This class of drugs has important pleiotropic effects as anti-inflammatory and antioxidant, providing numerous beneficial effects as cardioprotectors and maintenance of hemodynamic status. The benefits of statins in sepsis are still widely questioned; there are still doubts to reach a consensus about its use as a therapeutic strategy. Recently in our laboratory, it was observed that in animals surviving sepsis, simvastatin was able to act as a neuroprotective in structures responsible for cognitive processes related to memory and learning. Thus, the objective of this project will be to evaluate the possible pleiotropic effects of simvastatin and the impact of this drug on microglial and astrocytic activation in rats surviving sepsis.