Pioglitazone ameliorates neuronal damage after traumatic brain injury via the PPARγ/NF-κB/IL-6 signaling pathway
Autor: | Geli Liu, Jie Xu, Changdong Wang, Chengfu Yuan, Xue Yan Jiang, Hong Chen, Zhu Yong, Zhaosi Zhang, Xiaochuan Sun, Yongbing Deng, Xiaoyan Deng |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
lcsh:QH426-470 PPARγ Traumatic brain injury Inflammation Pharmacology Biochemistry Neuroprotection Article Cerebral edema Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Medicine Interleukin 6 Molecular Biology Genetics (clinical) Neuroinflammation lcsh:R5-920 IL-6 biology Pioglitazone business.industry Cell Biology medicine.disease nervous system diseases lcsh:Genetics 030104 developmental biology chemistry p-NF-κB biology.protein medicine.symptom business lcsh:Medicine (General) 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Genes & Diseases Genes and Diseases, Vol 7, Iss 2, Pp 253-265 (2020) |
ISSN: | 2352-3042 |
Popis: | 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. Keywords: Traumatic brain injury, IL-6, Pioglitazone, PPARγ, p-NF-κB |
Databáze: | OpenAIRE |
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