eCite Digital Repository
The microtubule-stabilizing drug Epothilone D increases axonal sprouting following transection injury in vitro
Citation
Brizuela, MD and Blizzard, CA and Chuckowree, JA and Dawkins, E and Gasperini, RJ and Young, KM and Dickson, TC, The microtubule-stabilizing drug Epothilone D increases axonal sprouting following transection injury in vitro, Molecular and Cellular Neurosciences, 66, (Part B) pp. 129-140. ISSN 1044-7431 (2015) [Refereed Article]
Copyright Statement
© 2015 Elsevier
DOI: doi:10.1016/j.mcn.2015.02.006
Abstract
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 Details
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 |
Downloads: | 0 |
Repository Staff Only: item control page