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 Bartlett Bunge; John L. Bixby; Frank Bradke

doi:10.1126/science.aaa2958

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 Bartlett Bunge, John L. Bixby, Frank Bradke

Research output: Contribution to journal › Article › peer-review

368 Scopus citations

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 language	English
Pages (from-to)	347-352
Number of pages	6
Journal	Science
Volume	348
Issue number	6232
DOIs	https://doi.org/10.1126/science.aaa2958
State	Published - 17 Apr 2015
Externally published	Yes

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Ruschel, J., Hellal, F., Flynn, K. C., Dupraz, S., Elliott, D. A., Tedeschi, A., Bates, M., Sliwinski, C., Brook, G., Dobrindt, K., Peitz, M., Brüstle, O., Norenberg, M. D., Blesch, A., Weidner, N., Bunge, M. B., Bixby, J. L., & 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

@article{6474892703594dd782676115cf76d7ae,

title = "Systemic administration of epothilone B promotes axon regeneration after spinal cord injury",

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.",

author = "J{\"o}rg Ruschel and Farida Hellal and Flynn, \{Kevin C.\} and Sebastian Dupraz and Elliott, \{David A.\} and Andrea Tedeschi and Margaret Bates and Christopher Sliwinski and Gary Brook and Kristina Dobrindt and Michael Peitz and Oliver Br{\"u}stle and Norenberg, \{Michael D.\} and Armin Blesch and Norbert Weidner and Bunge, \{Mary Bartlett\} and Bixby, \{John L.\} and Frank Bradke",

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doi = "10.1126/science.aaa2958",

language = "English",

volume = "348",

pages = "347--352",

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publisher = "American Association for the Advancement of Science",

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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, JL & 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

TY - JOUR

T1 - Systemic administration of epothilone B promotes axon regeneration after spinal cord injury

AU - Ruschel, Jörg

AU - Hellal, Farida

AU - Flynn, Kevin C.

AU - Dupraz, Sebastian

AU - Elliott, David A.

AU - Tedeschi, Andrea

AU - Bates, Margaret

AU - Sliwinski, Christopher

AU - Brook, Gary

AU - Dobrindt, Kristina

AU - Peitz, Michael

AU - Brüstle, Oliver

AU - Norenberg, Michael D.

AU - Blesch, Armin

AU - Weidner, Norbert

AU - Bunge, Mary Bartlett

AU - Bixby, John L.

AU - Bradke, Frank

PY - 2015/4/17

Y1 - 2015/4/17

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84927715105

U2 - 10.1126/science.aaa2958

DO - 10.1126/science.aaa2958

M3 - Article

C2 - 25765066

AN - SCOPUS:84927715105

SN - 0036-8075

VL - 348

SP - 347

EP - 352

JO - Science

JF - Science

IS - 6232

ER -

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

Abstract

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