Neuronal cytoskeletal alterations, in particular the loss and misalignment of microtubules, are considered a hallmark feature of the degeneration that occurs after traumatic brain injury (TBI). Therefore, microtubule-stabilizing drugs are attractive potential therapeutics for use following TBI. The best-known drug in this category is Paclitaxel, a widely used anti-cancer drug that has produced promising outcomes when employed in the treatment of various animal models of nervous system trauma. However, Paclitaxel is not ideal for the treatment of patients with TBI due to its limited blood-brain barrier (BBB) permeability. Herein we have characterized the effect of the brain penetrant microtubule-stabilizing agent Epothilone D (Epo D) on post-injury axonal sprouting in an in vitro model of CNS trauma. Epo D was found to modulate axonal sprout number in a dose dependent manner, increasing the number of axonal sprouts generated post-injury. Elevated sprouting was observed when analyzing the total population of injured neurons, as well as in selective analysis of Thy1-YFP-labeled excitatory neurons. However, we found no effect of Epo D on axonal sprout length or outgrowth speed. These findings indicate that Epo D specifically affects injury-induced axonal sprout generation, but not net growth. Our investigation demonstrates that primary cultures of cortical neurons are tolerant of Epo D exposure, and that Epo D significantly increases their regenerative response following structural injury. Therefore Epo D may be a potent therapeutic for enhancing regeneration following CNS injury. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.

Item Type:	Refereed Article
Keywords:	axotomy, Epothilone D, microtubule-stabilizing drug, microtubules, traumatic brain injury
Research Division:	Biomedical and Clinical Sciences
Research Group:	Neurosciences
Research Field:	Cellular nervous system
Objective Division:	Expanding Knowledge
Objective Group:	Expanding knowledge
Objective Field:	Expanding knowledge in the biological sciences
UTAS Author:	Brizuela, MD (Ms Mariana Brizuela)
UTAS Author:	Blizzard, CA (Dr Catherine Blizzard)
UTAS Author:	Chuckowree, JA (Dr Jyoti Chuckowree)
UTAS Author:	Dawkins, E (Dr Edgar Dawkins)
UTAS Author:	Gasperini, RJ (Dr Rob Gasperini)
UTAS Author:	Young, KM (Associate Professor Kaylene Young)
UTAS Author:	Dickson, TC (Professor Tracey Dickson)
ID Code:	100022
Year Published:	2015
Funding Support:	National Health and Medical Research Council (1045240)
Web of Science® Times Cited:	29
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2015-04-23
Last Modified:	2017-11-06
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