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Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPAR?/NF-?B/IL-6 signaling pathway.

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 (PPAR?) that can reduce inflammation following TBI. Clinically, neuroinflammation after TBI lacks effective treatment. Although there are many studies on PPAR? 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 PPAR?, IL-6, and p-NF-?B to identify the mechanisms of neuroinflammation. Then, in the rat TBI model, neurobehavioral and cerebral edema levels were investigated after intervention with pioglitazone (PPAR? activator) or T0070907 (PPAR? inhibitor), and PPAR?, IL-6 and p-NF-?B 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 PPAR? 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 PPAR? and reducing NF-?B and IL-6. The neuroprotective effect of pioglitazone on TBI was mediated through the PPAR?/NF-?B/IL-6 pathway.

SUBMITTER: Deng Y

PROVIDER: S-EPMC7083749 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Deng Yongbing Y Jiang Xue X Deng Xiaoyan X Chen Hong H Xu Jie J Zhang Zhaosi Z Liu Geli G Yong Zhu Z Yuan Chengfu C Sun Xiaochuan X Wang Changdong C

Genes & diseases 20190606 2

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 ...[more]

PMID: 32215295

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Dataset Information

Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPAR?/NF-?B/IL-6 signaling pathway.

Publications

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

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