{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:58:10Z","timestamp":1791979090717,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Alexander S. Onassis Public Benefit Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The molecular cascades involved in the induction and maintenance of neuroinflammation resulting from chronic compression of the cervical spinal cord in the setting of degenerative cervical myelopathy (DCM) have yet to be defined. Here, we determined the role of the fractalkine receptor, CX3CR1, during the neuroinflammatory response in a novel mouse model of DCM and demonstrated the relevance of this mechanism with human DCM tissue. Methods: Using our murine DCM model alongside the CX3CR1-knockout mice and a neutralizing antibody of CX3CR1 in wild-type mice, we examined protein, neurobehavioural and immunohistochemical readouts. The animal data were then complemented with immunohistochemical results from human post-mortem spinal cord tissue from individuals with DCM. Results: Humans and mice with DCM exhibited an up-regulation of CX3CR1 as well as markers of activated microglia\/macrophages in the cervical spinal cord. Knockout and neutralization of CX3CR1 hindered microglia\/macrophage activation and accumulation at the site of spinal cord compression. DCM mice exhibited decreased body speed and increased stance phase duration, which mirrors human DCM gait deficits. Strikingly, both CX3CR1 deficiency and CX3CR1 neutralization alleviated these gait deficits in DCM mice. Conclusions: Collectively, these data provide strong evidence that CX3CR1 plays a critical role in the secondary injury of neural structures in the setting of DCM. Further, targeting of CX3CR1 represents a promising therapeutic strategy to enhance neurological outcomes in DCM.<\/jats:p>","DOI":"10.3390\/jcm15010082","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T16:41:19Z","timestamp":1766594479000},"page":"82","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Examination of the Role of CX3CR1 in the Pathobiology of Degenerative Cervical Myelopathy: Evidence from Human and Mouse Tissue"],"prefix":"10.3390","volume":"15","author":[{"given":"Wen Ru","family":"Yu","sequence":"first","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon K.","family":"Karadimas","sequence":"additional","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sadat","sequence":"additional","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Brockie","sequence":"additional","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9885-3076","authenticated-orcid":false,"given":"Pia M.","family":"Vidal","sequence":"additional","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0616-7082","authenticated-orcid":false,"given":"Tim-Rasmus","family":"Kiehl","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathobiology, Neuroscience Program, University of Toronto, Toronto, ON M56 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Poulin","sequence":"additional","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1019-3670","authenticated-orcid":false,"given":"Aikaterini K.","family":"Andreopoulou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Patras, University Campus Rio, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5864-2047","authenticated-orcid":false,"given":"Joannis K.","family":"Kallitsis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Patras, University Campus Rio, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5722-6364","authenticated-orcid":false,"given":"Michael G.","family":"Fehlings","sequence":"additional","affiliation":[{"name":"Division of Genetics & Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, Canada"},{"name":"Division of Neurosurgery and Spinal Program, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1177\/1073858412467377","article-title":"Cervical Spondylotic Myelopathy: The Clinical Phenomenon and the Current Pathobiology of an Increasingly Prevalent and Devastating Disorder","volume":"19","author":"Karadimas","year":"2013","journal-title":"Neuroscientist"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s00586-014-3264-4","article-title":"Pathobiology of cervical spondylotic myelopathy","volume":"24","author":"Karadimas","year":"2015","journal-title":"Eur. 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