Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. (-)-Epigallocatechin-3-gallate (EGCG) has shown robust neuroprotective effects on various brain injury models in rodents. Herein, we aimed to investigate if EGCG protects against TBI and unravel the underlying mechanisms. A total of 102 mice were used for this study. TBI was induced by controlled cortical impact (CCI). EGCG was given immediately after TBI injury. Neurological functions were accessed by corner test, paw placement, modified neurological severity score, rotarod test, and Morris water maze test. AMPK inhibitor and AMPKα1-knockout mice were used to further study the signaling pathways involved in the observed effects. Our results show that EGCG significantly ameliorated CCI-induced neurological impairment, including spatial learning and memory. EGCG suppressed CCI-induced inflammation and oxidative stress. Furthermore, EGCG downregulated the phosphorylation of IKKα/β, IκBα, and nuclear translocation of NF-κB p65; upregulated AMPK phosphorylation; and altered corresponding changes in the phosphorylation of the downstream target’s ribosomal protein S6, AS160, and CaMKKß. Our data demonstrate that EGCG protects against CCI-induced TBI through the activation of the AMPK pathway in mice, suggesting that EGCG might be a promising therapeutic intervention preventing locomotor and cognitive impairments after TBI.
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Yinyin Wu and Jing Cui conceptualized the study and conducted the literature review for all databases. Jing Cui performed all statistical analyses. Yinyin Wu drafted the paper.
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All animal procedures were in accordance with the Guide for the Care and Use of Laboratory Animals (8th edition, NIH) and approved by The Second People’s Hospital of Hefei City.
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Wu, Y., Cui, J. (-)-Epigallocatechin-3-gallate provides neuroprotection via AMPK activation against traumatic brain injury in a mouse model. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2209–2220 (2020). https://doi.org/10.1007/s00210-020-01841-1
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DOI: https://doi.org/10.1007/s00210-020-01841-1