title: Taxol facilitates axon regeneration in the mature CNS.
abstract: Mature retinal ganglion cells (RGCs) cannot normally regenerate axons into the injured optic nerve but can do so after lens injury. Astrocyte-derived ciliary neurotrophic factor and leukemia inhibitory factor have been identified as essential key factors mediating this effect. However, the outcome of this regeneration is still limited by inhibitors associated with the CNS myelin and the glial scar. The current study demonstrates that Taxol markedly enhanced neurite extension of mature RGCs and PC12 cells by stabilization of microtubules and desensitized axons toward myelin and chondroitin sulfate proteoglycan (CSPG) inhibition in vitro without reducing RhoA activation. In vivo, the local application of Taxol at the injury site of the optic nerve of rats enabled axons to regenerate beyond the lesion site but did not affect the intrinsic regenerative state of RGCs. Furthermore, Taxol treatment markedly increased lens injury-mediated axon regeneration in vivo, delayed glial scar formation, suppressed CSPG expression, and transiently reduced the infiltration of macrophages at the injury site. Thus, microtubule-stabilizing compounds such as Taxol might be promising candidates as adjuvant drugs in the treatment of CNS injuries particularly when combined with interventions stimulating the intrinsic regenerative state of neurons.
authors.affiliation: Department of Neurology, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Vetrivel
authors.initials: V
authors.lastname: Sengottuvel
authors.forename: Marco
authors.initials: M
authors.lastname: Leibinger
authors.forename: Mariana
authors.initials: M
authors.lastname: Pfreimer
authors.forename: Anastasia
authors.initials: A
authors.lastname: Andreadaki
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fischer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001369:Axons / Q000187:drug effects*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D020221:Optic Nerve Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D020932:Nerve Growth Factor; D017239:Paclitaxel; D050257:Tubulin Modulators; D020742:rhoA GTP-Binding Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule