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Here, we report that GDNF enhanced both the number and caliber of regenerated axons <jats:italic>in vivo<\/jats:italic> and increased neurite outgrowth of dorsal root ganglion neurons (DRGN) <jats:italic>in vitro<\/jats:italic>, suggesting that GDNF has a direct effect on neurons. In SC\u2010DRGN coculture, GDNF significantly increased the number of myelin sheaths produced by SCs. GDNF treatment had no effect on the proliferation of isolated SCs but enhanced the proliferation of SCs already in contact with axons. GDNF increased the expression of the 140 kDa neural cell adhesion molecule (NCAM) in isolated SCs but not their expression of the adhesion molecule L1 or the secretion of the neurotrophins NGF, NT3, or BDNF. Overall, these results support the hypothesis that GDNF\u2010enhanced axonal regeneration and SC myelination is mediated mainly through a direct effect of GDNF on neurons. They also suggest that the combination of GDNF administration and SC transplantation may represent an effective strategy to promote axonal regeneration and myelin formation after injury in the spinal cord. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20840","type":"journal-article","created":{"date-parts":[[2009,1,23]],"date-time":"2009-01-23T19:12:24Z","timestamp":1232737944000},"page":"1178-1191","source":"Crossref","is-referenced-by-count":156,"title":["GDNF\u2010enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons"],"prefix":"10.1002","volume":"57","author":[{"given":"Liqun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George 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