{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:51:38Z","timestamp":1782399098541,"version":"3.54.5"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Secondary injury cascades critically influence neurological outcomes after severe spinal cord injury (SCI), yet effective disease-modifying pharmacological interventions remain lacking. Extracellular ATP\u2013mediated activation of the P2X7 receptor is a key driver of post-traumatic neuroinflammation, glial activation, and progressive tissue loss. While P2X7 receptor antagonism improves functional recovery in experimental rodent models of SCI, its translational relevance in naturally occurring large-animal injury has not been established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective, uncontrolled, exploratory observational study in client-owned dogs serving as a naturally occurring large-animal model of severe SCI. Twenty non-ambulatory dogs with cervical or thoracolumbar SCI whose owners declined surgical decompression received intravenous Brilliant Blue G (BBG), a selective P2X7 receptor antagonist, at 10\u202fmg\/kg\/day for seven consecutive days. Neurological function was assessed longitudinally using deep pain perception testing and the modified Frankel scale. Magnetic resonance imaging (MRI) was performed in a subset of cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Consistent neurological improvement temporally associated with BBG administration was observed across the cohort during follow-up. Eighteen dogs (90%) regained independent ambulation within 5\u202fdays to 15\u202fmonths (median, 4\u202fweeks). Among dogs presenting with complete injury equivalents (modified Frankel grade 5), 13 of 14 (92.9%; 95% CI, 66.1\u201399.8%) achieved independent ambulation. In cases with follow-up MRI, substantial functional recovery occurred despite persistent spinal cord compression. No adverse events attributable to BBG were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Systemic P2X7 receptor antagonism with BBG was feasible and well tolerated and was associated with substantial functional recovery in a naturally occurring large-animal model of severe SCI, even in the absence of surgical decompression. Although causality cannot be established in this uncontrolled study, the consistency of recovery patterns and the observation of improvement despite persistent mechanical compression support further investigation of P2X7 receptor inhibition as a disease-modifying therapeutic strategy for acute human SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1827771","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:28:26Z","timestamp":1781065706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["P2X7 receptor antagonism with Brilliant Blue G promotes functional recovery in spontaneous canine spinal cord injury: a preliminary study in a large animal model"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuhei","family":"Shimada","sequence":"first","affiliation":[{"name":"Sakuradai Animal Hospital","place":["Yokohama, Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/1751-0147-46-79","article-title":"Surgical decompression in dogs with thoracolumbar intervertebral disc disease and loss of deep pain perception: a retrospective study of 46 cases","volume":"46","author":"Laitinen","year":"2005","journal-title":"Acta Vet Scand"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13028-021-00596-w","article-title":"Investigation of timing of surgery and other factors possibly influencing outcome in dogs with acute thoracolumbar disc extrusion: a retrospective study of 1501 cases","volume":"63","author":"Immekeppel","year":"2021","journal-title":"Acta Vet Scand"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"12489","DOI":"10.1073\/pnas.0902531106","article-title":"Systemic administration of an 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receptor","volume":"158","author":"Roman","year":"2009","journal-title":"Br J Pharmacol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.2460\/javma.241.12.1617","article-title":"Long-term neurologic outcome of hemilaminectomy and disk fenestration for treatment of dogs with thoracolumbar intervertebral disk herniation: 831 cases (2000-2007)","volume":"241","author":"Aikawa","year":"2012","journal-title":"J Am Vet Med Assoc"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.tvjl.2016.12.008","article-title":"Proportion recovery and times to ambulation for non-ambulatory dogs with thoracolumbar disc extrusions treated with hemilaminectomy or conservative treatment: a systematic review and meta-analysis of case-series studies","volume":"220","author":"Langerhuus","year":"2017","journal-title":"Vet J"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1111\/jvim.17149","article-title":"Recovery of ambulation in small, nonbrachycephalic dogs after conservative management of acute thoracolumbar disk extrusion","volume":"38","author":"Khan","year":"2024","journal-title":"J Vet Intern Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/vru.13325","article-title":"Residual volume of extruded disc material and residual spinal cord compression measured on postoperative MRI do not predict neurological outcomes in dogs following decompressive surgery for thoracolumbar intervertebral disc extrusion","volume":"65","author":"Auffret","year":"2024","journal-title":"Vet Radiol Ultrasound"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1406843","DOI":"10.3389\/fvets.2024.1406843","article-title":"Outcome in paraplegic dogs with or without pain perception due to thoracolumbar fibrocartilaginous embolic myelopathy or acute non-compressive nucleus pulposus extrusion","volume":"11","author":"Togawa","year":"2024","journal-title":"Front Vet Sci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.bbr.2011.09.015","article-title":"Spinal P2X(7) receptor mediates microglia activation-induced neuropathic pain in the sciatic nerve injury rat model","volume":"226","author":"He","year":"2012","journal-title":"Behav Brain Res"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"648","DOI":"10.3171\/2020.7.SPINE20293","article-title":"Association of intravenous administration of human muse cells with deficit amelioration in a rat model of spinal cord injury","volume":"34","author":"Kajitani","year":"2021","journal-title":"J Neurosurg Spine"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"14603","DOI":"10.3390\/ijms241914603","article-title":"Intravenous administration of human muse cells ameliorates deficits in a rat model of subacute spinal cord injury","volume":"24","author":"Takahashi","year":"2023","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in 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