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Adelson Medical Research Foundation","doi-asserted-by":"publisher","award":["NIH 2 R01 NS038153\u201015"],"award-info":[{"award-number":["NIH 2 R01 NS038153\u201015"]}],"id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009152","name":"Fondation Bertarelli","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009152","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Motor axons in peripheral nerves have the capacity to regenerate after injury. However, full functional motor recovery rarely occurs clinically, and this depends on the nature and location of the injury. Recent preclinical findings suggest that there may be a time after nerve injury where, while regrowth to the muscle successfully occurs, there is nevertheless a failure to re\u2010establish motor function, suggesting a possible critical period for synapse reformation. We have now examined the temporal and anatomical determinants for the re\u2010establishment of motor function after prolonged neuromuscular junction (NMJ) denervation in rats and mice. Using both sciatic transection\u2013resuture and multiple nerve crush models in rats and mice to produce prolonged delays in reinnervation, we show that regenerating fibres reach motor endplates and anatomically fully reform the NMJ even after extended periods of denervation. However, in spite of this remarkably successful anatomical regeneration, after 1\u00a0month of denervation there is a consistent failure to re\u2010establish functional recovery, as assessed by behavioural and electrophysiological assays. We conclude that this represents a failure in re\u2010establishment of synaptic function, and the possible mechanisms responsible are discussed, as are their clinical implications.<\/jats:p>","DOI":"10.1111\/ejn.13059","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T11:42:07Z","timestamp":1441194127000},"page":"451-462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Lack of motor recovery after prolonged denervation of the neuromuscular junction is not due to regenerative failure"],"prefix":"10.1111","volume":"43","author":[{"given":"Miyuki","family":"Sakuma","sequence":"first","affiliation":[{"name":"Department of Neurobiology Harvard Medical School Boston MA 02115 USA"},{"name":"Kirby Neurobiology Center Boston Children's Hospital Boston MA 02115 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