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Erythropoietin Protects Rat Brain Injury from Carbon Monoxide Poisoning by Inhibiting Toll-Like Receptor 4/NF-kappa B-Dependent Inflammatory Responses

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Abstract

Inflammatory responses play critical roles in carbon monoxide (CO) poisoning-induced cerebral injury. The present study investigated whether erythropoietin (EPO) modulates the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) inflammatory signaling pathways in brain injury after acute CO poisoning. EPO (2500 and 5000 U/kg) was injected subcutaneously twice a day after acute CO poisoning for 2 days. At 48 h after treatment, the expression levels of TLR4 and NF-κB as well as the levels of inflammatory cytokines in the hippocampal tissues were measured. Our results showed that CO poisoning induced a significant upregulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat hippocampal tissues. Treatment with EPO remarkably suppressed the gene and protein expression levels of TLR4 and NF-κB, as well as the concentrations of TNF-α, IL-1β, and IL-6 in the hippocampal tissues. EPO treatment ameliorated CO poisoning-induced histological edema and neuronal necrosis. These results suggested that EPO protected against CO poisoning-induced brain damage by inhibiting the TLR4–NF-κB inflammatory signaling pathway.

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Acknowledgments

This study was supported by research grants from the National Natural Science Foundation of China (No. 81501653, No. 81401581) and the Science and Technology Development Plan of Jilin Province (No. 201201042). We thank Medjaden Bioscience Limited for assisting in the preparation of this manuscript.

Authors’ Contributions

Xiang-Wei Meng and Ping Zhang developed the study design and coordinated its implementation, and were responsible for data collection. Li Pang, Ning Dong, and Da-Hai Xu carried out laboratory tests. Nan Zhang and Da-Wei Wang carried out the statistical analysis. Li Pang and Nan Zhang drafted the manuscript. All authors read and approved the final manuscript.

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    Authors and Affiliations

    1. Department of Emergency, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China

      Li Pang, Nan Zhang, Ning Dong, Da-Wei Wang & Da-Hai Xu

    2. Graduate Management Office, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China

      Ping Zhang

    3. Department of Gastrointestinal Medicine, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China

      Xiang-Wei Meng

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    1. Li Pang
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    Li Pang and Nan Zhang contributed equally to this work.

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    Pang, L., Zhang, N., Dong, N. et al. Erythropoietin Protects Rat Brain Injury from Carbon Monoxide Poisoning by Inhibiting Toll-Like Receptor 4/NF-kappa B-Dependent Inflammatory Responses. Inflammation 39, 561–568 (2016). https://doi.org/10.1007/s10753-015-0280-4

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