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

Abstract：

: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 (naïve, 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-β, 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 Ser396-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.

journal_name

Neurotox Res

journal_title

Neurotoxicity research

authors

Catalão CHR,Santos-Junior NN,da Costa LHA,Souza AO,Cárnio EC,Sebollela A,Alberici LC,Rocha MJA

doi

10.1007/s12640-020-00222-z

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

871-886

issue

eissn

1029-8428

issn

1476-3524

pii

10.1007/s12640-020-00222-z

journal_volume

pub_type

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