Required growth facilitators propel axon regeneration across complete spinal cord injury.

Nature
Mark A AndersonMichael V Sofroniew

Abstract

Transected axons fail to regrow across anatomically complete spinal cord injuries (SCI) in adults. Diverse molecules can partially facilitate or attenuate axon growth during development or after injury1-3, but efficient reversal of this regrowth failure remains elusive4. Here we show that three factors that are essential for axon growth during development but are attenuated or lacking in adults-(i) neuron intrinsic growth capacity2,5-9, (ii) growth-supportive substrate10,11 and (iii) chemoattraction12,13-are all individually required and, in combination, are sufficient to stimulate robust axon regrowth across anatomically complete SCI lesions in adult rodents. We reactivated the growth capacity of mature descending propriospinal neurons with osteopontin, insulin-like growth factor 1 and ciliary-derived neurotrophic factor before SCI14,15; induced growth-supportive substrates with fibroblast growth factor 2 and epidermal growth factor; and chemoattracted propriospinal axons with glial-derived neurotrophic factor16,17 delivered via spatially and temporally controlled release from biomaterial depots18,19, placed sequentially after SCI. We show in both mice and rats that providing these three mechanisms in combination, but not indi...Continue Reading

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Methods Mentioned

BETA
dot blot
fluorescence microscopy
transgenic
X-ray
dot blots
immunoprecipitation
RNA Assay
PCR
HT-seq

Software Mentioned

Bioconductor EdgeR
ImageJ
StereoInvestigator
PowerLab
Imaris
NIH ImageJ
STAR aligner
GraphPad
LabChart Pro
NeuroLucida

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