Modulation of microtubule stability as a strategy for promoting axonal regeneration after spinal roo

来源 :Joint Symposium of 2016 International Neural Regeneration Sy | 被引量 : 0次 | 上传用户:cyx810625
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  Spinal root avulsion is featured by the rupture site located in the CNS/PNS interface,with close proximity to the neuronal cell bodies.The injured motoneurons have to form new growth cones and extend their axons through long distance before they can reinnervate their target muscles.Due to limited neuronal intrinsic regrowth speed and the inhibitory scar in the CNS/PNS transitional zone,prolonged regeneration often leads to muscle atrophy and motor dysfunction.The assembly of new growth cones and axonal elongation require the reorganization of cytoskeleton and efficient axonal transportation.Micro-tubule participants in these regenerative processes.In addition,microtubule stabilization by Epothilone B (EpoB) facilitates axonal regeneration after spinal cord injury,probably due to enhanced polymerization of tubulin dimers.In the present study,we hypothesized that following spinal root avulsion injury,microtubule stabilization could promote axons to go throu gh the suppressive transitional zone and achieve faster regeneration.Adult rats underwent cervical ventral root avulsion (C5-7),followed by re-implantation of C6,before being treated with EpoB or dimethyl sulfoxide as vehicle control.We demonstrated that: 1) EpoB application significantly promoted motor functional recovery,indicated by higher Terzis grooming test score of EpoB treatment group (Figure 1).2) Electrophysiologically healthier motor units were found in animals administrated with EpoB,as suggested by electromyography.EpoB reduced spontaneous potentials,which were generated by denervated muscle fibers (Figure 2A),while higher electrical responses (Figure 2B and C) were provoked in the same group.3) At 9 weeks post surgery,more cells regenerated their axons into distal musculocutaneous nerve as displayed by retrograde labeling using Flu-orogold.72.5% more cells were labeled in animals treated with EpoB (Figure 3).4) In the inhibitory transitional zone,EpoB facilitated direct axonal elongation,whereas axons in vehicle group took meandering courses with more turns.In addition,EpoB enabled more choline acetyltransferase-positive axons to regenerate in the transitional zone.Our results show that mi-crotubule stabilization by EpoB is a potential strategy for promoting axonal regeneration and functional recovery after spinal root avulsion.
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