Simvastatin improves intracerebral hemorrhage through NF‑κB‑mediated apoptosis via the MyD88/TRIF signaling pathway

  • Authors:
    • Chengyao Gu
    • Yunqin Wu
    • Zhenyi Fan
    • Weiwei Han
  • View Affiliations

  • Published online on: October 23, 2017     https://doi.org/10.3892/etm.2017.5349
  • Pages:377-382
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Abstract

The aim was to investigate the neuroprotective effects and potential mechanism mediated by simvastatin in a mouse model of intracerebral hemorrhage. CD‑1 mice were subjected to infusion of collagenase type IV into the left striatum in order to induce intracerebral hemorrhage. Western blot analysis, the TUNEL assay and the modified neurological severity score were used in the present study to analyze the efficacy of simvastatin for intracerebral hemorrhage. The results demonstrated that simvastatin treatment improved the cerebral water content and blood‑brain barrier disruption in the intracerebral hemorrhage animals. Intracerebral hemorrhage‑induced neuronal cell death was downregulated by simvastatin treatment compared with the vehicle‑treated model group. In addition, the expression levels of aquaporin‑4, matrix metallopeptidase 9 and caspase‑3 were downregulated and B‑cell lymphoma‑2 was upregulated by simvastatin treatment compared with the vehicle‑treated model. Simvastatin treatment also significantly reduced the Evans blue leakage into the injured hemispheres and improved motor function. Mechanism analysis further indicated that simvastatin treatment downregulated nuclear factor (NF)‑κB expression, and upregulated the myeloid differentiation primary response 88 (MyD88) and TIR domain‑containing adaptor protein inducing interferon‑β (TRIF) expression levels in neuronal cells in experimental mice. Furthermore, the results revealed that NF‑κB overexpression abolished the simvastatin‑downregulated MyD88 and TRIF expression levels, as well as the apoptosis of neuronal cells. In conclusion, these results indicated that simvastatin was able to attenuate brain edema and reduce cellular apoptosis by suppressing the NF‑κB‑mediated MyD88/TRIF signaling pathway subsequent to the induction of intracerebral hemorrhage in mice.

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January 2018
Volume 15 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

2016 Impact Factor: 1.261
Ranked #50/128 Medicine Research and Experimental
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APA
Gu, C., Wu, Y., Fan, Z., & Han, W. (2018). Simvastatin improves intracerebral hemorrhage through NF‑κB‑mediated apoptosis via the MyD88/TRIF signaling pathway. Experimental and Therapeutic Medicine, 15, 377-382. https://doi.org/10.3892/etm.2017.5349
MLA
Gu, C., Wu, Y., Fan, Z., Han, W."Simvastatin improves intracerebral hemorrhage through NF‑κB‑mediated apoptosis via the MyD88/TRIF signaling pathway". Experimental and Therapeutic Medicine 15.1 (2018): 377-382.
Chicago
Gu, C., Wu, Y., Fan, Z., Han, W."Simvastatin improves intracerebral hemorrhage through NF‑κB‑mediated apoptosis via the MyD88/TRIF signaling pathway". Experimental and Therapeutic Medicine 15, no. 1 (2018): 377-382. https://doi.org/10.3892/etm.2017.5349