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Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration

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Autor(es):
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
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: NEUROTOXICITY RESEARCH; v. 38, n. 4, p. 16-pg., 2020-06-10.
Resumo

Sepsis-associated encephalopathy causes brain dysfunction that can result in cognitive impairments in sepsis survivor patients. In previous work, we showed that simvastatin attenuated oxidative stress in brain structures related to memory in septic rats. However, there is still a need to evaluate the long-term impact of simvastatin administration on brain neurodegenerative processes and cognitive damage in sepsis survivors. Here, we investigated the possible neuroprotective role of simvastatin in neuroinflammation, and neurodegeneration conditions of brain structures related to memory in rats at 10 days after sepsis survival. Male Wistar rats (250-300 g) were submitted to cecal ligation and puncture (CLP,n = 42) or remained as non-manipulated (naive,n = 30). Both groups were treated (before and after the surgery) by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline and observed for 10 days. Simvastatin-treated rats that survived to sepsis showed a reduction in the levels of nitrate, IL1-beta, and IL-6 and an increase in Bcl-2 protein expression in the prefrontal cortex and hippocampus, and synaptophysin only in the hippocampus. Immunofluorescence revealed a reduction of glial activation, neurodegeneration, apoptosis, and amyloid aggregates confirmed by quantification of GFAP, Iba-1, phospho Ser(396)-tau, total tau, cleaved caspase-3, and thioflavin-S in the prefrontal cortex and hippocampus. In addition, treated animals presented better performance in tasks involving habituation memory, discriminative, and aversive memory. These results suggest that statins exert a neuroprotective role by upregulation of the Bcl-2 and gliosis reduction, which may prevent the cognitive deficit observed in sepsis survivor animals. (AU)

Processo FAPESP: 18/10089-2 - Controle neural, hormonal e nutricional da autofagia
Beneficiário:Isis Do Carmo Kettelhut
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/12462-0 - Estudo do efeito neuroprotetor da sinvastatina nas disfunções cognitivas em animais sobreviventes à sepse
Beneficiário:Carlos Henrique Rocha Catalão
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 18/02854-0 - Avaliação da ativação glial nas alterações neuroimunoendócrinas em ratos sépticos e efeito neuroprotetor da sinvastatina nos sobreviventes
Beneficiário:Maria José Alves da Rocha
Modalidade de apoio: Auxílio à Pesquisa - Regular