Glial activation analysis in the neuroimmunoendocrine alterations in septic rats and the simvastatin neuroprotector effect in survivals

• Grant number: 18/02854-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2018
• End date: December 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria José Alves da Rocha
• Grantee: Maria José Alves da Rocha
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Evelin Capellari Cárnio ; Luciane Carla Alberici ; Norberto Cysne Coimbra
• Associated scholarship(s): 18/20944-7 - Evaluation of glial activation in neuroimmunoendocrine alterations in septic rats and neuroprotective effect of simvastatin in survivors, BP.TT

Abstract

Sepsis, a systemic inflammation triggered by an infectious agent, produces an inflammatory state in the central nervous system (CNS) that leads to autonomic, endocrine and cognitive-behavioral dysfunctions observed in clinical and experimental studies. Previous findings from this laboratory suggest that oxidative stress, microglial activation, synaptic dysfunction and eventually apoptosis of neurons due to neuroinflammation and with neurodegenerative characteristics are responsible for these dysfunctions during and after sepsis. Thus, we suggest that sustained glial activation during sepsis would cause neuroimmunoendocrine changes and long-term neurological sequelae, leading to the establishment of neurodegenerative processes such as those occurring in the sporadic form of Alzheimer's disease. In this context, numerous drugs and therapies have been proposed to try to contain the effects of sepsis. For example, several clinical studies involving statins and sepsis are still very controversial about the benefits of this drug, leaving many gaps to be filled in order to reach a consensus on its use as a therapeutic strategy. Recently we have found that simvastatin improved the cognitive-behavioral aspects of rats survival sepsis. However, if the sepsis improvement is related to an effect of the drug in neurodegeneration and/or modulation of glial activation is unknown. Recently, we have found that simvastatin treatment improved the cognitive-behavioral aspects of rats surviving sepsis. Therefore, the objective of this study will be to evaluate the participation of glial activation in the neuroimmunoendocrine changes due to sepsis and the possible neuroprotective effect of simvastatin in surviving animals. (AU)

Scientific publications

(4)

(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)

DA COSTA, LUIS HENRIQUE ANGENENDT; SANTOS-JUNIOR, NILTON NASCIMENTO; CATALAO, CARLOS HENRIQUE ROCHA; ROCHA, MARIA JOSE ALVES. Microglial Activation Modulates Neuroendocrine Secretion During Experimental Sepsis. Molecular Neurobiology, v. 58, n. 5, JAN 2021. (18/02854-0, 16/07803-0)

VULCZAK, ANDERSON; ROCHA CATALAO, CARLOS HENRIQUE; PEDRO DE FREITAS, LUIZ ALEXANDRE; ALVES ROCHA, MARIA JOSE. HSP-Target of Therapeutic Agents in Sepsis Treatment. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 17, SEP 1 2019. (18/02854-0)

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)