• Xiupeng Xu, Tongle Zhi, Honglu Chao, Kuan Jiang, Yinlong Liu, Zhongyuan Bao, Liang Fan, Dong Wang, Zheng Li, Ning Liu, and Jing Ji.
• Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
• Bba Mol Basis Dis. 2018 May 1; 1864 (5 Pt A): 1663-1674.

AbstractAcute lung injury (ALI) is one of several complications in patients with traumatic brain injury (TBI). Autophagy is a primary homeostatic process that promotes cell survival under stress. Accumulating evidence implicates autophagy in the pathogenesis of ALI under various conditions. However, the role of autophagy in TBI-induced ALI remains unknown. The aim of this study was to adjust autophagy with pharmacological agents to determine its functional significance in TBI-induced ALI. Rats were preconditioned with autophagy promoter rapamycin or inhibitor 3-methyladenine before they were challenged with TBI. Extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126, mechanistic target of rapamycin (mTOR) inhibitor rapamycin, and signal transducer and activator of transcription 3 (Stat3) inhibitor S31-201 were used to test the role of ERK1/2/mTOR/Stat3 signaling pathway in regulating autophagy. Autophagy is activated in lung tissues after TBI. Enhancement of autophagy suppressed apoptosis, inflammation and oxidative stress in lung tissues, which were activated after TBI, whereas inhibition of autophagy aggravated these critical pathological changes. Autophagy also improved TBI-induced impairment in pulmonary barrier function, oxygenation function and static compliance. Furthermore, TBI-induced autophagy was mediated by ERK1/2/mTOR/Stat3 pathway, which may serve to reduce ALI and improve pulmonary barrier function, oxygenation function and static compliance. These findings are important for the prevention and treatment of TBI-induced ALI.Copyright © 2018 Elsevier B.V. All rights reserved.

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