title: Etanercept, an inhibitor of TNF-a, prevents propofol-induced neurotoxicity in the developing brain.
abstract: Propofol can induce acute neuronal apoptosis, neuronal loss or long-term cognitive impairment when exposed in neonatal rodents, but the mechanisms by which propofol induces developmental neurotoxicity are unclear. Recent studies have demonstrated that propofol can increase the TNF-α level in the developing brain, but there is a lack of direct evidence to show whether TNF-α is partially or fully involved in propofol-induced neurotoxicity. The present study shows that propofol exposure in neonatal rats induces an increase of TNF-α in the cerebral spinal fluid, hippocampus and prefrontal cortex (PFC). Etanercept, a TNF-α inhibitor, prevents propofol-induced short- or long-term neuronal apoptosis, neuronal loss, synaptic loss and long-term cognitive impairment. Furthermore, mTNF-α (precursor of TNF-α) expression in microglia cells is increased after propofol anaesthesia in either the hippocampus or PFC, but mTNF-α expression in neurons is only increased in the PFC. These findings suggest that TNF-α may mediate propofol-induced developmental neurotoxicity, and etanercept can provide neural protection. Microglia are the main cellular source of TNF-α after propofol exposure, while the synthesis of TNF-α in neurons is brain-region selective.
authors.affiliation: Department of Anesthesiology, Chongqing Cancer Institute, Chongqing 40030, PR China; Guangxi Medical University, Nanning, Guangxi 530021, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Chongqing Cancer Institute, Chongqing 40030, PR China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Deng
authors.affiliation: Institute of Life Science, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Chongqing Cancer Institute, Chongqing 40030, PR China. Electronic address: liuhl75@163.com.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept / Q000627:therapeutic use*; D006993:Hypnotics and Sedatives / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008660:Metabolism / Q000187:drug effects; D008840:Microfilament Proteins / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D015742:Propofol / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: C100745:Aif1 protein, rat; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002135:Calcium-Binding Proteins; D006993:Hypnotics and Sedatives; D008840:Microfilament Proteins; D016708:Synaptophysin; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D000068800:Etanercept; D015742:Propofol
keywords: Developing brain; Etanercept; Neuroinflammation; Neurotoxicity; Propofol; TNF-α