Study of the neuroprotective effect of simvastatin on cognitive impairments in sepsis surviving animals

• Grant number: 17/12462-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2019
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria José Alves da Rocha
• Grantee: Carlos Henrique Rocha Catalão
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 21/06496-4 - Systemic inflammation mediated by sepsis promotes Alzheimer's Disease pathology in animal models, BE.EP.PD

Abstract

The installation of an inflammatory process in the CNS, even in the absence of in situ infection, is commonly referred to as sepsis-associated encephalopathy (SAE). This condition is responsible for brain dysfunction that will result in functional and cognitive impairment in sepsis surviving patients. Although the cognitive disabilities found in sepsis survivors should not be equated with those found in common dementias, such as Alzheimer's disease (AD), the presence of certain similar characteristics, such as permanent deficits and specificity for regions responsible for mnemonic processes, are intriguing and suggest common underlying mechanisms between them. In the last decade, evidence indicates that neurodegeneration is associated with the presence of neuroinflammation in various CNS disorders. Our hypothesis is that SAE memory deficits found in sepsis survivors originate from neurodegenerative processes associated with sustained neuroinflammation. In this context, several drugs and therapies have been proposed with the aim to contain the effects of severe sepsis and septic shock, among them statins. However, the several clinical studies are still very controversial about the benefits of statins in this context and many gaps must still be filled to reach a consensus on their use in therapeutic strategies. Therefore, our objective will be to investigate the occurrence of neurodegenerative processes in memory signaling pathways and the possible neuroprotective effect of simvastatin administered prior and continuously to sepsis surviving animals. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROCHA CATALAO, CARLOS HENRIQUE; SOUZA, ANDERSON DE OLIVEIRA; SANTOS-JUNIOR, NILTON NASCIMENTO; ANGENENDT DA COSTA, LUIS HENRIQUE; DOS SANTOS, JONATHAS RODRIGO; ALBERICI, LUCIANE CARLA; ALVES ROCHA, MARIA JOSE. Pre-treatment and continuous administration of simvastatin during sepsis improve metabolic parameters and prevent CNS injuries in survivor rats. Molecular and Cellular Biochemistry, v. N/A, p. 11-pg., 2022-05-23. (17/12462-0)

DA COSTA, LUIS HENRIQUE ANGENENDT. Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration. NEUROTOXICITY RESEARCH, JUN 2020. (18/10089-2, 18/02854-0, 17/12462-0)

CATALAO, CARLOS HENRIQUE ROCHA; SANTOS-JUNIOR, NILTON NASCIMENTO; DA COSTA, LUIS HENRIQUE ANGENENDT; SOUZA, ANDERSON OLIVEIRA; CARNIO, EVELIN CAPELLARI; SEBOLLELA, ADRIANO; ALBERICI, LUCIANE CARLA; ROCHA, MARIA JOSE ALVES. Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration. NEUROTOXICITY RESEARCH, v. 38, n. 4, p. 16-pg., 2020-06-10. (18/10089-2, 17/12462-0, 18/02854-0)