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Given the context\u2010dependent pro\u2010inflammatory or neuroprotective actions of interferon\u2010\u03b3 (IFN\u2010\u03b3), this study investigated its role in an in\u00a0vitro model of oxaliplatin\u2010induced neurotoxicity (OIPN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rat organotypic spinal cord slices were exposed to oxaliplatin to model chemotherapy\u2010induced neurotoxicity responses in\u00a0vitro. IFN\u2010\u03b3 cytotoxicity was assessed at 6 and 24\u2009h. Neurotoxicity, inflammatory mediators, neurotrophic factors, and markers of glial and neuronal activation were analyzed by biochemical and immunohistochemical assays. Connexin 43 (Cx43) was assessed using Gap19 and Gap27 to probe hemichannel and gap\u2010junction contributions. Electrophysiological recordings characterized neuronal excitability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IFN\u2010\u03b3 (6.5\u2013200\u2009ng\/mL) was non\u2010toxic and, at 65\u2009ng\/mL, significantly reduced oxaliplatin\u2010induced neurotoxicity, decreasing LDH release and suppressing pro\u2010inflammatory mediators (CCL2, SerpinA3N, CGRP, substance P, c\u2010Fos). IFN\u2010\u03b3 modulated its signaling by reducing IFN\u03b3R and increasing IRF1 expression. It prevented oxaliplatin\u2010induced overexpression of neurotrophic factors and reduced glial and neuronal hyperactivation markers, preserving neuronal integrity. IFN\u2010\u03b3 reduced Cx43 expression and hemichannel activity, and Gap19 reproduced selected protective effects. Electrophysiology showed attenuation of oxaliplatin\u2010induced neuronal hyperexcitability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IFN\u2010\u03b3 attenuates oxaliplatin\u2010induced neurotoxic responses in an in\u00a0vitro spinal cord model. The parallel reduction in Cx43 expression and hemichannel activity supports further investigation of Cx43 signaling as a candidate pharmacological target in OIPN.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71197","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:01:28Z","timestamp":1792652488000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interferon\u2010\u03b3 Mitigates Oxaliplatin\u2010Induced Neurotoxicity: Analogies With Connexin 43"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8435-6017","authenticated-orcid":false,"given":"Alessandra","family":"Toti","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence 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