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Atorvastatin Relieves Cognitive Disorder After Sepsis Through Reverting Inflammatory Cytokines, Oxidative Stress, and Neuronal Apoptosis in Hippocampus

  • Jianmei Tian
  • Yongjie Tai
  • Mengrao Shi
  • Chunxiu Zhao
  • Wenwen Xu
  • Xuhua GeEmail author
  • Guoji ZhuEmail author
Original Research

Abstract

This present research work reports the possible effects and the underlying mechanism of atorvastatin on survival rate and cognitive disorders after sepsis. Sepsis is a life-threatening dysfunction that arises when the body’s response to infection causes injury to its own tissues and organs. Diffuse sepsis was induced by cecal ligation and puncture surgery (CLP) in ICR mice. 0.2 mg/kg body weight of atorvastatin was administrated intraperitoneally at 12 h before surgery. The survival of mice was calculated 24 h, 48 h, 72 h, and 96 h after CLP surgery. Two weeks later, open-field test and Morris water maze test were conducted to evaluate the protective effect of atorvastatin. Inflammatory cytokines in plasma, oxidative stress parameters, number of astrocytes, and neuronal cell deaths in the CA3 region of the hippocampus were examined using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. The results indicate that pretreatment with atorvastatin can increase survival percentage and improve cognitive function. Atorvastatin reversed all these alterations in parallel with a decrease in circulating levels of cytokines (IL-1β, IL-4, IL-6, and TNF-α) in plasma, inhibited the activities of oxidative stress parameters (lower TBARS levels, ratio of GSH/GSSH, and activities of SOD and CAT), enhanced the activity of citrate synthase in brain, and reduced the number of astrocytes and neuronal cell deaths in CA3 region of hippocampus. Overall, our results indicated that atorvastatin exhibited protective effects on survival rate and cognitive disorders after sepsis by inhibiting the release of inflammatory cytokines, oxidative stress, and neuronal apoptosis in brain tissue.

Keywords

Atorvastatin Sepsis Inflammation Oxidative stress Apoptosis 

Notes

Funding

This work was supported by the Jiangsu province natural science foundation of China (BK20151204).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Neonate DepartmentSoochow University Affiliated Children’s HospitalSuzhouPeople’s Republic of China
  2. 2.Department of Internal MedicineSoochow University Affiliated Children’s HospitalSuzhouPeople’s Republic of China
  3. 3.Department of General Medicine, Department of General Practice of Tongji UniversityYangpu Hospital Tongji University School of MedicineShanghaiPeople’s Republic of China

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