(-)-Epigallocatechin-3-gallate provides neuroprotection via AMPK activation against traumatic brain injury in a mouse mo
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ORIGINAL ARTICLE
(-)-Epigallocatechin-3-gallate provides neuroprotection via AMPK activation against traumatic brain injury in a mouse model Yinyin Wu 1 & Jing Cui 1 Received: 11 December 2019 / Accepted: 6 February 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 AMPKα1knockout 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. Keywords (-)-Epigallocatechin-3-gallate . Controlled cortical impact . Neurological function . Inflammation . Oxidative stress . AMPK
Introduction Traumatic brain injury (TBI) causes long-term disability and death for millions. It remains an enormous societal and economic burden (Maas et al. 2017). Two stages of brain injuries, primary and secondary brain injuries, are classified in TBI (Kaur and Sharma 2018; Pearn et al. 2017; Pushkarna et al. 2010). Of which, primary injury is caused at the time of the initial damage force, including tissue destruction and distortion in the early post-injury period. Secondary injury occurs from hours to days to months after the initial trauma. It is the result of disturbance of brain and systemic physiology following the traumatic event, such as the formation of cerebral Yinyin Wu and Jing Cui contributed equally to this work. * Yinyin Wu [email protected] 1
The Second People’s Hospital of Hefei City, Intersection of Guangde Road and Leshui Road, Yaohai District, Hefei 230011, Anhui, China
edema, intracranial hematoma, depolarization, excitotoxicity, metabolic abnormalities, and disruption of the blood-brain barrier. Since very few can be done to influence the primary injury, traditional treatment strategies mainly focused on the intervention of secondary brain injuries. However, many potentia
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