title: Erythropoietin Protects Rat Brain Injury from Carbon Monoxide Poisoning by Inhibiting Toll-Like Receptor 4/NF-kappa B-Dependent Inflammatory Responses.
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.
authors.affiliation: Department of Emergency, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Emergency, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Emergency, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.affiliation: Department of Emergency, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Department of Emergency, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China.
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Xu
authors.affiliation: Graduate Management Office, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China. 187211618@qq.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Medicine, The First Hospital of Jilin University, 71 Xinmin Road, Changchun, 130021, China. xiangweimeng2003@163.com.
authors.forename: Xiang-Wei
authors.initials: XW
authors.lastname: Meng
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology*; D002248:Carbon Monoxide / Q000633:toxicity*; D002249:Carbon Monoxide Poisoning / Q000473:pathology*; D004487:Edema / Q000517:prevention & control*; D004921:Erythropoietin / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009336:Necrosis / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C000599851:erythropoietin, rat; D004921:Erythropoietin; D002248:Carbon Monoxide
keywords: carbon monoxide poisoning; erythropoietin; inflammatory cytokine; nuclear factor-kappa B; toll-like receptor 4