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Initial calcium release from intracellular stores followed by calcium dysregulation is linked to secondary axotomy following transient axonal stretch injury

Citation

Staal, JA and Dickson, TC and Gasperini, R and Liu, Y and Foa, L and Vickers, JC, Initial calcium release from intracellular stores followed by calcium dysregulation is linked to secondary axotomy following transient axonal stretch injury, Journal of Neurochemistry, 112, (5) pp. 1147-1155. ISSN 0022-3042 (2010) [Refereed Article]


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The definitive published version is available online at: http://interscience.wiley.com

DOI: doi:10.1111/j.1471-4159.2009.06531.x

Abstract

Acute axonal shear and stretch in the brain induces an evolving form of axonopathy and is a major cause of ongoing motor, cognitive and emotional dysfunction. We have utilized an in vitro model of mild axon bundle stretch injury, in cultured primary cortical neurons, to determine potential early critical cellular alterations leading to secondary axonal degeneration. We determined that transient axonal stretch injury induced an initial acute increase in intracellular calcium, principally derived from intracellular stores, which was followed by a delayed increase in calcium over 48 h post-injury (PI). This progressive and persistent increase in intracellular calcium was also associated with increased frequency of spontaneous calcium fluxes as well as cytoskeletal abnormalities. Additionally, at 48 h post-injury, stretch-injured axon bundles demonstrated filopodia-like sprout formation that preceded secondary axotomy and degeneration. Pharmacological inhibition of the calcium-activated phosphatase, calcineurin, resulted in reduced secondary axotomy (p < 0.05) and increased filopodial sprout length. In summary, these results demonstrate that stretch injury of axons induced an initial substantial release of calcium from intracellular stores with elevated intracellular calcium persisting over 2 days. These long-lasting calcium alterations may provide new insight into the earliest neuronal abnormalities that follow traumatic brain injury as well as the key cellular changes that lead to the development of diffuse axonal injury and secondary degeneration.

Item Details

Item Type:Refereed Article
Keywords:calcineurin, diffuse axonal injury, intracellular calcium disruption, neuronal stretch injury, secondary axotomy, traumatic brain injury
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Staal, JA (Dr Jerome Staal)
Author:Dickson, TC (Professor Tracey Dickson)
Author:Gasperini, R (Dr Rob Gasperini)
Author:Liu, Y (Professor Yongbing Liu)
Author:Foa, L (Professor Lisa Foa)
Author:Vickers, JC (Professor James Vickers)
ID Code:64013
Year Published:2010
Web of Science® Times Cited:45
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-06-16
Last Modified:2014-12-17
Downloads:0

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