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Exp Neurol. 2018 Aug;306:250-259. doi: 10.1016/j.expneurol.2018.01.018. Epub 2018 Feb 2.

Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats.

Author information

1
Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstrasse 200 a, 69118 Heidelberg, Germany.
2
Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
3
Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstrasse 200 a, 69118 Heidelberg, Germany; Stark Neurosciences Research Institute, Indiana University School of Medicine, Department of Neurological Surgery and Goodman Campbell Brain and Spine, 320 West 15th Street, NB 500B, Indianapolis, IN 46202, United States.
4
Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstrasse 200 a, 69118 Heidelberg, Germany. Electronic address: norbert.weidner@med.uni-heidelberg.de.

Abstract

Following a spinal cord injury (SCI) a growth aversive environment forms, consisting of a fibroglial scar and inhibitory factors, further restricting the already low intrinsic growth potential of injured adult central nervous system (CNS) neurons. Previous studies have shown that local administration of the microtubule-stabilizing drug paclitaxel or epothilone B (Epo B) reduce fibrotic scar formation and axonal dieback as well as induce axonal growth/sprouting after SCI. Likewise, systemic administration of Epo B promoted functional recovery. In this study, we investigated the effects of epothilone D (Epo D), an analog of Epo B with a possible greater therapeutic index, on fibrotic scarring, axonal sprouting and functional recovery after SCI. Delayed systemic administration of Epo D after a moderate contusion injury (150 kDyn) in female Fischer 344 rats resulted in a reduced number of footfalls when crossing a horizontal ladder at 4 and 8 weeks post-injury. Hindlimb motor function assessed with the BBB open field locomotor rating scale and Catwalk gait analysis were not significantly altered. Moreover, formation of laminin positive fibrotic scar tissue and 5-HT positive serotonergic fiber length caudal to the lesion site were not altered after treatment with Epo D. These findings recapitulate a functional benefit after systemic administration of a microtubule-stabilizing drug in rat contusion SCI.

KEYWORDS:

Epothilone D; Functional recovery; Microtubule stability; Moderate contusion; Spinal cord injury

PMID:
29408734
DOI:
10.1016/j.expneurol.2018.01.018
[Indexed for MEDLINE]

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