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Citation |
Tehse J, Taghibiglou C. Eur. J. Neurosci. 2019; 49(9): 1157-1170. |
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Affiliation |
Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N 5E5, Canada. |
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Copyright |
(Copyright © 2019, Federation of European Neuroscience Societies, Publisher John Wiley and Sons) |
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DOI |
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PMID |
30554430 |
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Abstract |
Traumatic brain injury (TBI) is a leading major cause of morbidity and mortality in youth and individuals under 45 year age. A wide variety of cellular and molecular mechanisms have been identified contributing to the pathogenesis of TBI. A better understanding of the pathophysiology behind TBI is essential for providing more effective treatment. Excitotoxicity as one of the secondary molecular events is a major contributing factor in apoptosis and neuronal death following the initial injury in TBI. Excitotoxicity is the rapid overload and influx of calcium into the cell cytoplasm, activating a series of deleterious signaling cascades causing the cell to undergo apoptosis. Conventional understanding is that the rapid influx of calcium is initiated through glutamate release. However, there are overlooked glutamate-independent mechanisms that cause the rapid calcium influx into the neuronal cytoplasm, evoking or contributing to excitotoxicity. Therefore, the focus of this review will be on the role of the glutamate-independent excitotoxic mechanisms of the mechanosensitive response of NMDA receptors, mechanoporation of the cell membrane, ischemia and the release of calcium from intracellular stores. In conclusion, the shear and stretch forces during a TBI event may result in the mechanosensitive activation of NMDA receptors which contribute to glutamate-independent excitotoxicity. This article is protected by copyright. All rights reserved. Language: en |
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Keywords |
brain ischemia; excitotoxicity; intracellular calcium stores; mechanoporation; traumatic brain injury |