Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway
Authors Liang J, Wu S, Xie W, He H
Received 16 December 2017
Accepted for publication 19 February 2018
Published 16 April 2018 Volume 2018:12 Pages 845—853
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Sukesh Voruganti
Jinwei Liang, Shanhu Wu, Wenxi Xie, Hefan He
Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China
Background: Ketamine can act as a multifunctional neuroprotective agent by inhibiting oxidative stress, cellular dysfunction, and apoptosis. Although it has been proven to be effective in various neurologic disorders, the mechanism of the treatment of traumatic brain injury (TBI) is not fully understood. The aim of this study was to investigate the neuroprotective function of ketamine in models of TBI and the potential role of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this putative protective effect.
Materials and methods: Wild-type male mice were randomly assigned to five groups: Sham group, Sham + ketamine group, TBI group, TBI + vehicle group, and TBI + ketamine group. Marmarou’s weight drop model in mice was used to induce TBI, after which either ketamine or vehicle was administered via intraperitoneal injection. After 24 h, the brain samples were collected for analysis.
Results: Ketamine significantly ameliorated secondary brain injury induced by TBI, including neurological deficits, brain water content, and neuronal apoptosis. In addition, the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were restored by the ketamine treatment. Western blotting and immunohistochemistry showed that ketamine significantly increased the level of Nrf2. Furthermore, administration of ketamine also induced the expression of Nrf2 pathway-related downstream factors, including hemeoxygenase-1 and quinine oxidoreductase-1, at the pre- and post-transcriptional levels.
Conclusion: Ketamine exhibits neuroprotective effects by attenuating oxidative stress and apoptosis after TBI. Therefore, ketamine could be an effective therapeutic agent for the treatment of TBI.
Keywords: traumatic brain injury, ketamine, oxidative stress, Nrf2, apoptosis
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