Systemic administration of epothilone B promotes axon regeneration after spinal cord injury

Jörg Ruschel, Farida Hellal, Kevin C. Flynn, Sebastian Dupraz, David A. Elliott, Andrea Tedeschi, Margaret Bates, Christopher Sliwinski, Gary Brook, Kristina Dobrindt, Michael Peitz, Oliver Brüstle, Michael D Norenberg, Armin Blesch, Norbert Weidner, Mary B Bunge, John Bixby, Frank Bradke

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

After central nervous system (CNS) injury, inhibitory factors in the lesion scar and poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier-permeable microtubule-stabilizing drug, epothilone B (epoB), decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug-elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury.

Original languageEnglish (US)
Pages (from-to)347-352
Number of pages6
JournalScience
Volume348
Issue number6232
DOIs
StatePublished - Apr 17 2015

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Spinal Cord Injuries
Axons
Regeneration
Cicatrix
Microtubules
Nervous System Trauma
Central Nervous System
Growth
Epothilones
Blood-Brain Barrier
Polymerization
Pharmaceutical Preparations
epothilone B
Rodentia
Fibroblasts

ASJC Scopus subject areas

  • General

Cite this

Ruschel, J., Hellal, F., Flynn, K. C., Dupraz, S., Elliott, D. A., Tedeschi, A., ... Bradke, F. (2015). Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science, 348(6232), 347-352. https://doi.org/10.1126/science.aaa2958

Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. / Ruschel, Jörg; Hellal, Farida; Flynn, Kevin C.; Dupraz, Sebastian; Elliott, David A.; Tedeschi, Andrea; Bates, Margaret; Sliwinski, Christopher; Brook, Gary; Dobrindt, Kristina; Peitz, Michael; Brüstle, Oliver; Norenberg, Michael D; Blesch, Armin; Weidner, Norbert; Bunge, Mary B; Bixby, John; Bradke, Frank.

In: Science, Vol. 348, No. 6232, 17.04.2015, p. 347-352.

Research output: Contribution to journalArticle

Ruschel, J, Hellal, F, Flynn, KC, Dupraz, S, Elliott, DA, Tedeschi, A, Bates, M, Sliwinski, C, Brook, G, Dobrindt, K, Peitz, M, Brüstle, O, Norenberg, MD, Blesch, A, Weidner, N, Bunge, MB, Bixby, J & Bradke, F 2015, 'Systemic administration of epothilone B promotes axon regeneration after spinal cord injury', Science, vol. 348, no. 6232, pp. 347-352. https://doi.org/10.1126/science.aaa2958
Ruschel J, Hellal F, Flynn KC, Dupraz S, Elliott DA, Tedeschi A et al. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science. 2015 Apr 17;348(6232):347-352. https://doi.org/10.1126/science.aaa2958
Ruschel, Jörg ; Hellal, Farida ; Flynn, Kevin C. ; Dupraz, Sebastian ; Elliott, David A. ; Tedeschi, Andrea ; Bates, Margaret ; Sliwinski, Christopher ; Brook, Gary ; Dobrindt, Kristina ; Peitz, Michael ; Brüstle, Oliver ; Norenberg, Michael D ; Blesch, Armin ; Weidner, Norbert ; Bunge, Mary B ; Bixby, John ; Bradke, Frank. / Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. In: Science. 2015 ; Vol. 348, No. 6232. pp. 347-352.
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