• Min Shen, Shan Wang, Xin Wen, Xin-Rui Han, Yong-Jian Wang, Xiu-Min Zhou, Man-He Zhang, Dong-Mei Wu, Jun Lu, and Yuan-Lin Zheng.
• Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, PR China.
• Biomed. Pharmacother. 2017 Nov 1; 95: 885-893.

ObjectiveThis study aims to explore the neuroprotective effects of dexmedetomidine (Dex) in rats suffering from traumatic brain injury (TBI) via the PI3K/Akt/mTOR signaling pathway.MethodsA weight drop model was performed for TBI model establishment. A total of 150 Sprague Dawley rats were selected and assigned into control, sham, TBI, TBI+Dex, TBI+LY294002 (LY) and TBI+Dex+LY groups. Modified Neurological Severity Score (mNSS) was conducted in order to evaluate the neurological injury. The water content in brain tissues was measured. The expressions of PI3K/Akt/mTOR signaling pathway-related proteins, tight junction proteins (ZO-1 and Claudin-5) and autophagy proteins (LC3 I/II and Beclin-1) were detected using Western blot assay. A TUNEL assay was applied for cell apoptosis, immunofluorescence was employed for the detection of the positive expression of LC3, and ELISA was applied for detection of levels of inflammatory factors [tumor necrosis factor-alph (TNF-a), interleukin-1β (IL-1β), interferon-γ (INF-γ) as well as IL-6], respectively.ResultsCompared with the control group, the other four groups exhibited increased mNSS, brain water content, expression of LC3, TNF-a, IL-1β, INF-γ and IL-6, and positive expression of LC3, expression of LC3 I/II and Beclin-1, but decreased expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5. Compared with the TBI group, the TBI+Dex group exhibited reduced mNSS, brain water content, expression of LC3, TNF-a, IL-1β, INF-γ and IL-6, positive expression of LC3, as well as expression of LC3 I/II and Beclin-1 but demonstrated an elevated expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5, while opposite trends were observed in the TBI+LY group. The TBI+Dex group exhibited reduced mNSS, brain water content, expression of LC3, TNF-a, IL-1β, INF-γ and IL-6, positive expression of LC3, as well as expression of LC3 I/II and Beclin-1 but demonstrated an elevated expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5, while opposite trends were observed in the TBI+LY group, as compared with the TBI+Dex+LY group.ConclusionThe data shows that Dex exerts a neuroprotective effect via the activation of the PI3K/Akt/mTOR signaling pathway in rats with TBI.Copyright © 2017. Published by Elsevier Masson SAS.

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