Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy
| العنوان: | Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy |
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| المؤلفون: | Ryan C. Turner, Brandon Lucke-Wold, John M. Lee, Julian E. Bailes, Charles L. Rosen, Matthew J. Robson, Linda Nguyen, Aric F. Logsdon, Bennet Omalu, Jason D. Huber |
| المصدر: | Journal of Neurosurgery. 124:687-702 |
| بيانات النشر: | Journal of Neurosurgery Publishing Group (JNSPG), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Traumatic brain injury, Football, Disease, Rats sprague dawley, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Blast Injuries, Brain Injury, Chronic, Animals, Humans, Medicine, Wrestling, business.industry, Endoplasmic reticulum, Neurodegeneration, General Medicine, Endoplasmic Reticulum Stress, medicine.disease, Rats, Sprague dawley, Disease Models, Animal, Chronic traumatic encephalopathy, 030104 developmental biology, DHA - Docosahexaenoic acid, business, 030217 neurology & neurosurgery |
| الوصف: | OBJECT Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors’ clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase–3β. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy. |
| تدمد: | 1933-0693 0022-3085 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96e9bfed5a3cb44a40593e3ef9126662Test https://doi.org/10.3171/2015.3.jns141802Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....96e9bfed5a3cb44a40593e3ef9126662 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19330693 00223085 |
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