{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:34:01Z","timestamp":1784774041427,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 NS081063"],"award-info":[{"award-number":["R01 NS081063"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Complete severance of major peripheral mixed sensory\u2013motor nerve proximally in a mammalian limb produces immediate loss of action potential conduction and voluntary behaviors mediated by the severed distal axonal segments. These severed distal segments undergo Wallerian degeneration within days. Denervated muscles atrophy within weeks. Slowly regenerating (\u223c1\u2009mm\/day) outgrowths from surviving proximal stumps that often nonspecifically reinnervate denervated targets produce poor, if any, restoration of lost voluntary behaviors. In contrast, in this study using completely transected female rat sciatic axons as a model system, we provide extensive morphometric, immunohistochemical, electrophysiological, and behavioral data to show that these adverse outcomes are avoided by microsuturing closely apposed axonal cut ends (neurorrhaphy) and applying a sequence of well\u2010specified solutions, one of which contains polyethylene glycol (PEG). This \u201cPEG\u2010fusion\u201d procedure within minutes reestablishes axoplasmic and axolemmal continuity and signaling by nonspecifically fusing (connecting) closely apposed open ends of severed motor and\/or sensory axons at the lesion site. These PEG\u2010fused axons continue to conduct action potentials and generate muscle action potentials and muscle twitches for months and do not undergo Wallerian degeneration. Continuously innervated muscle fibers undergo much less atrophy compared with denervated muscle fibers. Dramatic behavioral recovery to near\u2010unoperated levels occurs within days to weeks, almost certainly by activating many central nervous system and peripheral nervous system synaptic and other plasticities, some perhaps to a greater extent than most neuroscientists would expect. Negative control transections in which neurorrhaphy and all solutions except the PEG\u2010containing solution are applied produce none of these remarkably fortuitous outcomes observed for PEG\u2010fusion.<\/jats:p>","DOI":"10.1002\/jnr.24225","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T15:10:25Z","timestamp":1523891425000},"page":"1223-1242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures, and behaviors lost after sciatic nerve transections in female rats"],"prefix":"10.1002","volume":"96","author":[{"given":"Michelle","family":"Mikesh","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2125-1186","authenticated-orcid":false,"given":"Cameron L.","family":"Ghergherehchi","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Molecular Biology University of Texas at Austin Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Louis","family":"Hastings","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Rahesh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Jagannath","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale R.","family":"Sengelaub","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences Indiana University Bloomington Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Trevino","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Wellspan Teaching Hospitals York Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Neuraptive Therapeutics Lafayette Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5610-6264","authenticated-orcid":false,"given":"George D.","family":"Bittner","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Texas at Austin Austin Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0749-0712(21)00502-3","article-title":"Functional results of primary nerve repair","volume":"16","author":"Allan C. H.","year":"2000","journal-title":"Hand Clinics"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1980.sp013465"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.180724"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhsa.2017.07.014"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000001203"},{"key":"e_1_2_10_7_1","first-page":"483","article-title":"Axon diameter and myelin sheath thickness in nerve fibres of the ventral spinal root of the seventh lumbar nerve of the adult and developing cat","volume":"136","author":"Berthold C. H.","year":"1983","journal-title":"Journal of Anatomy"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23023"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.177716"},{"key":"e_1_2_10_10_1","first-page":"12","article-title":"Conundrums and confusions regarding how PEG\u2010fusion produces excellent behavioral recovery after peripheral nerve injuries","author":"Bittner G. D.","year":"2017","journal-title":"Neural Regeneration Research"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23849"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23685"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.05.020"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01051.2009"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06631.2002"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780195169904.001.0001"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4160-5279-1.00032-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2008.03.018"},{"key":"e_1_2_10_19_1","first-page":"611","article-title":"Quantitating integrated muscle function following reinnervation","volume":"37","author":"Carlton J. M.","year":"1986","journal-title":"Surgical Forum"},{"key":"e_1_2_10_20_1","volume-title":"Statistical power analysis for the behavioral sciences","author":"Cohen J.","year":"1998"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1964.sp007369"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-201102001-00002"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(82)90234-5"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(83)90276-5"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)00156-B"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(86)90125-1"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23704"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7233"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4160-5279-1.00001-0"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1943.sp004002"},{"key":"e_1_2_10_31_1","first-page":"15","article-title":"The re\u2010innervation of muscle after various periods of atrophy","volume":"78","author":"Gutmann E.","year":"1944","journal-title":"Journal of Anatomy"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10130"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.61"},{"key":"e_1_2_10_34_1","volume-title":"Principles of neural science","author":"Kandel E. R.","year":"2013"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0621-07.2007"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.12.041"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-11-06638.1994"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-006-0097-z"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-07-02442.1999"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880141113"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00378-6"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1095862"},{"key":"e_1_2_10_43_1","article-title":"Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats","author":"Mikesh M.","year":"2018","journal-title":"Journal of Neuroscience Research"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1968.0012"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn905"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01206897"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23514"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/SAP.0000000000001242"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23734"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23867"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.04.082"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.07.015"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13059"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.22.1.389"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.22237\/jmasm\/1257035100"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1995.1010"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2012.03.049"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11552-015-9780-9"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4814-11.2012"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3339-13.2013"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4155-10.2010"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23022"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e31814934d8"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6484"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/micr.20156"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2011.04.008"}],"updated-by":[{"DOI":"10.1002\/jnr.24277","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T00:00:00Z","timestamp":1532390400000}}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.24225","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.24225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T12:40:05Z","timestamp":1694954405000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.24225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,16]]},"references-count":66,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1002\/jnr.24225"],"URL":"https:\/\/doi.org\/10.1002\/jnr.24225","archive":["Portico"],"relation":{"correction":[{"id-type":"doi","id":"10.1002\/jnr.24277","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,16]]},"assertion":[{"value":"2017-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}