title: Axonal regeneration. 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.
authors.affiliation: Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ruschel
authors.affiliation: Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Farida
authors.initials: F
authors.lastname: Hellal
authors.affiliation: Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Flynn
authors.affiliation: Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dupraz
authors.affiliation: Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: David A
authors.initials: DA
authors.lastname: Elliott
authors.affiliation: Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tedeschi
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 Northwest 14th Terrace, Miami, FL33136, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Bates
authors.affiliation: Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sliwinski
authors.affiliation: Institute for Neuropathology, RWTH Aachen University, Steinbergweg 20, 52074, Aachen, Germany. Jülich-Aachen Research Alliance-Translational Brain Medicine.
authors.forename: Gary
authors.initials: G
authors.lastname: Brook
authors.affiliation: Institute of Reconstructive Neurobiology, Life&Brain Center, University of Bonn and Hertie Foundation, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Dobrindt
authors.affiliation: Institute of Reconstructive Neurobiology, Life&Brain Center, University of Bonn and Hertie Foundation, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Peitz
authors.affiliation: Institute of Reconstructive Neurobiology, Life&Brain Center, University of Bonn and Hertie Foundation, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.affiliation: Departments of Pathology, Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Norenberg
authors.affiliation: Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Blesch
authors.affiliation: Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstr. 200A, 69118 Heidelberg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Weidner
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 Northwest 14th Terrace, Miami, FL33136, USA.
authors.forename: Mary Bartlett
authors.initials: MB
authors.lastname: Bunge
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1095 Northwest 14th Terrace, Miami, FL33136, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Bixby
authors.affiliation: Axonal Growth and Regeneration, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. frank.bradke@dzne.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Bradke
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology / Q000517:prevention & control*; D034261:Epothilones / Q000008:administration & dosage*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008578:Meninges / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D050257:Tubulin Modulators / Q000008:administration & dosage*
chemical_list: D034261:Epothilones; D050257:Tubulin Modulators; C093788:epothilone B