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Cyclosporin - a treatment attenuates delayed cytoskeletal alterations and secondary axotomy following mild axonal stretch injury


Staal, JA and Dickson, TC and Chung, RS and Vickers, JC, Cyclosporin - a treatment attenuates delayed cytoskeletal alterations and secondary axotomy following mild axonal stretch injury, Developmental Neurobiology, 67, (14) pp. 1831-1842. ISSN 1932-8451 (2007) [Refereed Article]

DOI: doi:10.1002/dneu.20552


Following central nervous system trauma, diffuse axonal injury and secondary axotomy result from a cascade of cellular alterations including cytoskeletal and mitochondrial disruption. We have examined the link between intracellular changes following mild/ moderate axonal stretch injury and secondary axotomy in rat cortical neurons cultured to relative maturity (21 days in vitro). Axon bundles were transiently stretched to a strain level between 103% and 106% using controlled pressurized fluid. Double-immunohistochemical analysis of neurofilaments, neuronal spectrin, α-internexin, cytochrome-c, and ubiquitin was conducted at 24-, 48-, 72-, and 96-h postinjury. Stretch injury resulted in delayed cytoskeletal damage, maximal at 48-h postinjury. Accumulation of cytochrome-c and ubiquitin was also evident at 48 h following injury and colocalized to axonal regions of cytoskeletal disruption. Pretreatment of cultures with cyclosporin-A, an inhibitor of calcineurin and the mitochondrial membrane transitional pore, reduced the degree of cytoskeletal damage in stretch-injured axonal bundles. At 48-h postinjury, 20% of untreated cultures demonstrated secondary axotomy, whereas cyclosporin A-treated axon bundles remained intact. By 72-h postinjury, 50% of control preparations and 7% of cyclosporin A-treated axonal bundles had progressed to secondary axotomy, respectively. Statistical analyses demonstrated a significant (p < 0.05) reduction in secondary axotomy between treated and untreated cultures. In summary, these results suggest that cyclosporin-A reduces progressive cytoskeletal damage and secondary axotomy following transient axonal stretch injury in vitro. © 2007 Wiley Periodicals, Inc.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Staal, JA (Dr Jerome Staal)
UTAS Author:Dickson, TC (Professor Tracey Dickson)
UTAS Author:Chung, RS (Associate Professor Roger Chung)
UTAS Author:Vickers, JC (Professor James Vickers)
ID Code:45098
Year Published:2007
Web of Science® Times Cited:28
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-08-01
Last Modified:2012-03-01

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