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Development of pharmacological interventions aimed at enhancing regeneration may improve this. One potential pharmacological target is the P2X purinergic receptor 7 (P2X7R) expressed in Schwann cells, which is known to play a role during the development of the peripheral nerves. Herein, we analysed differences in regeneration between genetically engineered P2X7 knockout mice and wild\u2010type controls, using in vivo and ex vivo models of peripheral nerve regeneration. We have found that the speed of axonal regeneration is unaltered in P2X7 knockout mice, nevertheless regenerated P2X7 knockout nerves are morphologically different to wild\u2010type nerves following transection and immediate repair. Indeed, the detailed morphometric analysis at 4 and 8\u00a0weeks after injury showed evidence of delayed remyelination in P2X7 knockout mice, compared to the wild\u2010type controls. Furthermore, the Wallerian degeneration phase was unaltered between the two experimental groups. We also analysed gene expression changes in the dorsal root ganglia neurones as a result of the peripheral nerve injury, and found changes in pathways related to pain, inflammation and cell death. We conclude that P2X7 receptors in Schwann cells may be a putative pharmacological target to control cell fate following injury, thus enhancing nerve re\u2010myelination.<\/jats:p>","DOI":"10.1111\/ejn.14995","type":"journal-article","created":{"date-parts":[[2020,10,4]],"date-time":"2020-10-04T09:33:57Z","timestamp":1601804037000},"page":"5798-5814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Peripheral nerve regeneration following injury is altered in mice lacking P2X7 receptor"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-7042","authenticated-orcid":false,"given":"Valerio","family":"Magnaghi","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Martin","sequence":"additional","affiliation":[{"name":"Blond McIndoe Laboratories Division of Cell Matrix Biology and Regenerative Medicine School of Biological Sciences Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Smith","sequence":"additional","affiliation":[{"name":"Blond McIndoe Laboratories Division of Cell Matrix Biology and Regenerative Medicine School of Biological Sciences Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke","family":"Allen","sequence":"additional","affiliation":[{"name":"Blond McIndoe Laboratories Division of Cell Matrix Biology and Regenerative Medicine School of Biological Sciences Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Conte","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1752-3302","authenticated-orcid":false,"given":"Adam J.","family":"Reid","sequence":"additional","affiliation":[{"name":"Blond McIndoe Laboratories Division of Cell Matrix Biology and Regenerative Medicine School of Biological Sciences Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre  Manchester UK"},{"name":"Department of Plastic Surgery &amp; 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