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Article

Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling

  • Authors:
    • Lijun Yin
    • Xuejun Chen
    • Hongbo Ji
    • Shunli Gao
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, P.R. China
  • Pages: 4731-4740
    |
    Published online on: October 1, 2019
       https://doi.org/10.3892/mmr.2019.10718
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Abstract

Sepsis‑associated encephalopathy (SAE) is characterized by neuronal apoptosis and changes in mental status. Accumulating evidence has. indicated that dexmedetomidine is capable of protecting the brain against external stimuli and improving cognitive dysfunctions. The aim of the present study was to investigate the possible neuroprotective effects of dexmedetomidine on SAE and the role of heat‑shock protein (Hsp)90/AKT signaling in an experimental model of sepsis. The SAE model was established by cecal ligation and perforation (CLP) in vivo and lipopolysaccharide (LPS) treated hippocampal neuronal cultures in vitro. It was found that dexmedetomidine inhibited caspase‑3, but increased the expression level ofBcl‑2 in CLP rats. CLP rats also exhibited a decreased level of phosphorylated AKT Thr 308 and Hsp90, and their expression could be reversed by treatment with dexmedetomidine. Additionally, application of dexmedetomidine increased cell survival and decreased neuronal apoptosis in vitro. Furthermore, the neuroprotective effects of dexmedetomidine could be reversed by 17‑AAG (a Hsp90 inhibitor), or wortmannin (a PI3K inhibitor). Analysis of TUNEL staining indicated that dexmedetomidine improved LPS‑induced neuronal apoptosis, which could be eradicated by AKT short hairpin RNA transfection, prazosin or yohimbine. Finally, dexmedetomidine ameliorated both the emotional and spatial cognitive disorders without alteration in locomotor activity. The present findings suggested that dexmedetomidine may protect the brain against SAE, and that the Hsp90/AKT pathway may be involved in this process.
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Copy and paste a formatted citation
Spandidos Publications style
Yin L, Chen X, Ji H and Gao S: Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling. Mol Med Rep 20: 4731-4740, 2019.
APA
Yin, L., Chen, X., Ji, H., & Gao, S. (2019). Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling. Molecular Medicine Reports, 20, 4731-4740. https://doi.org/10.3892/mmr.2019.10718
MLA
Yin, L., Chen, X., Ji, H., Gao, S."Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling". Molecular Medicine Reports 20.5 (2019): 4731-4740.
Chicago
Yin, L., Chen, X., Ji, H., Gao, S."Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling". Molecular Medicine Reports 20, no. 5 (2019): 4731-4740. https://doi.org/10.3892/mmr.2019.10718
Copy and paste a formatted citation
x
Spandidos Publications style
Yin L, Chen X, Ji H and Gao S: Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling. Mol Med Rep 20: 4731-4740, 2019.
APA
Yin, L., Chen, X., Ji, H., & Gao, S. (2019). Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling. Molecular Medicine Reports, 20, 4731-4740. https://doi.org/10.3892/mmr.2019.10718
MLA
Yin, L., Chen, X., Ji, H., Gao, S."Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling". Molecular Medicine Reports 20.5 (2019): 4731-4740.
Chicago
Yin, L., Chen, X., Ji, H., Gao, S."Dexmedetomidine protects against sepsis‑associated encephalopathy through Hsp90/AKT signaling". Molecular Medicine Reports 20, no. 5 (2019): 4731-4740. https://doi.org/10.3892/mmr.2019.10718
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