Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway

Yongbing Deng; Xue Jiang; Xiaoyan Deng; Hong Chen; Jie Xu; Zhaosi Zhang; Geli Liu; Zhu Yong; Chengfu Yuan; Xiaochuan Sun; Changdong Wang

doi:10.1016/j.gendis.2019.05.002

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Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway

Full-length article | 更新时间：2022-06-24

- Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway
- Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway
- Genes & Diseases 2020年7卷第2期
- 作者机构：
  
  1. Department of Neurosurgery of the First Affiliated Hospital of Chongqing Medical University, Yixueyuan Road #1,Chongqing,PR China,400016
  2. Department of Neurosurgery of the Chongqing Emergency Medical Center, Jiankang Road #1,Chongqing,PR China,400014
  3. Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Yixueyuan Road #1,Chongqing,PR China,400016
  4. Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, Irvine,CA,USA,92697
  5. College of Medical Science, China Three Gorges University,Hubei,Yichang,PR China,443002
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2019.05.002
  中图分类号：
- 纸质出版日期：2020，
  
  网络出版日期：2020-6-1，
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Yongbing Deng, Xue Jiang, Xiaoyan Deng, 等. Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway[J]. Genes & Diseases, 2020,7(2).

Yongbing Deng, Xue Jiang, Xiaoyan Deng, et al. Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway[J]. Genes & Diseases, 2020,7(2).
Yongbing Deng, Xue Jiang, Xiaoyan Deng, 等. Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway[J]. Genes & Diseases, 2020,7(2). DOI： 10.1016/j.gendis.2019.05.002.

Yongbing Deng, Xue Jiang, Xiaoyan Deng, et al. Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway[J]. Genes & Diseases, 2020,7(2). DOI： 10.1016/j.gendis.2019.05.002.

摘要

Abstract

Traumatic brain injury (TBI) is the major cause of high mortality and disability rates worldwide. Pioglitazone is an activator of peroxisome proliferator-activated receptor-gamma (PPARγ) that can reduce inflammation following TBI. Clinically

neuroinflammation after TBI lacks effective treatment. Although there are many studies on PPARγ in TBI animals

only few could be converted into clinical

since TBI mechanisms in humans and animals are not completely consistent. The present study

provided a potential theoretical basis and therapeutic target for neuroinflammation treatment after TBI. First

we detected interleukin-6 (IL-6)

nitric oxide (NO) and Caspase-3 in TBI clinical specimens

confirming a presence of a high expression of inflammatory factors. Western blot (WB)

quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to detect PPARγ

IL-6

and p-NF-κB to identify the mechanisms of neuroinflammation. Then

in the rat TBI model

neurobehavioral and cerebral edema levels were investigated after intervention with pioglitazone (PPARγ activator) or T0070907 (PPARγ inhibitor)

and PPARγ

IL-6 and p-NF-κB were detected again by qRT-PCR

WB and immunofluorescence (IF). The obtained results revealed that: 1) increased expression of IL-6

NO and Caspase-3 in serum and cerebrospinal fluid in patients after TBI

and decreased PPARγ in brain tissue; 2) pioglitazone could improve neurobehavioral and reduce brain edema in rats after TBI; 3) the protective effect of pioglitazone was achieved by activating PPARγ and reducing NF-κB and IL-6. The neuroprotective effect of pioglitazone on TBI was mediated through the PPARγ/NF-κB/IL-6 pathway.

关键词

Keywords

Traumatic brain injuryIL-6PioglitazonePPARγp-NF-κB

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