• Wei Jin, Jun Wu, Handong Wang, Jie Kong, Hongbin Ni, and Weibang Liang.
• Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
• J Trauma. 2011 Sep 1;71(3):680-6.

BackgroundIn our previous studies, antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has been shown to play an important role in protecting traumatic brain injury (TBI)-induced acute lung injury (ALI). This study was designed to explore whether recombinant human erythropoietin (rhEPO) administration modulates pulmonary Nrf2 signaling pathway in a murine TBI model.MethodsClosed head injury was made by Hall's weight-dropping method. The rhEPO was administered at a dose of 5,000 IU/kg 30 minutes after TBI. Pulmonary capillary permeability, wet or dry weight ratio, apoptosis, Nrf2 and its downstream cytoprotective enzymes including NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase were investigated at 24 hours after TBI.ResultsWe found that treatment with rhEPO markedly ameliorated TBI-induced ALI, as characterized by decreased pulmonary capillary permeability, wet or dry weight ratio, and alveolar cells apoptosis. Administration of rhEPO also significantly upregulated the mRNA expressions and activities of Nrf2 signaling pathway-related agents, including Nrf2, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase.ConclusionsThe results of this study suggest that post-TBI rhEPO administration may induce Nrf2-mediated cytoprotective response in the lung, and this may be a mechanism whereby rhEPO reduces TBI-induced ALI.

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