{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:55:54Z","timestamp":1782917754275,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FORDECYT-PRONACES","award":["845110"],"award-info":[{"award-number":["845110"]}]},{"name":"Postdoctoral Fellowship Program of SECIHTI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: This study aimed to investigate the effect of tibolone (TIB) on the expression of the NOX2 and NOX4 isoforms and their co-localization in neurons and astrocytes using an animal model of spinal cord injury (SCI). Methods: Male Sprague Dawley rats were subjected to contusive SCI at T9 and treated with TIB (1 or 2.5 mg\/kg\/day). The expression of NOX2 and NOX4, and their co-localization in neurons and astrocytes, were evaluated at 3, 7, and 15 days post-SCI. Oxidative stress markers and motor recovery were also assessed. Results: SCI induced a time-dependent increase in NOX2 protein expression at 15 days compared to 3 days (0.192 \u00b1 0.012 vs. 0.013 \u00b1 0.0007) and in NOX4 protein expression (0.027 \u00b1 0.002 vs. 0.958 \u00b1 0.088), displaying differential cell-specific localization patterns in neurons and astrocytes across time points. TIB treatment significantly attenuated SCI-induced oxidative stress (15,391.8 \u00b1 1047.6 vs. 21,264.4 \u00b1 2669.8) and decreased NOX2 and NOX4 co-localization in both neurons and astrocytes in a dose- and time-dependent manner. Furthermore, TIB-treated animals exhibited a modest but significant restoration of motor function at 15 days post-SCI. Conclusions: Our findings indicate that TIB administration reduces oxidative stress, modifies NOX2 and NOX4 immunoreactivity patterns in neurons and astrocytes, and promotes partial functional recovery following SCI.<\/jats:p>","DOI":"10.3390\/brainsci16070711","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:41:38Z","timestamp":1782909698000},"page":"711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tibolone Administration Is Associated with Enhanced Motor Recovery and Decreased Cell-Specific NOX2 and NOX4 Immunoreactivity in a Rat Model of Traumatic Spinal Cord Injury"],"prefix":"10.3390","volume":"16","author":[{"given":"Tzayaka","family":"Castillo-Mendieta","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, Hospital de Especialidades Dr. Bernardo Sep\u00falveda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0508-5221","authenticated-orcid":false,"given":"Stephanie","family":"S\u00e1nchez-Torres","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, Hospital de Especialidades Dr. Bernardo Sep\u00falveda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0715-9263","authenticated-orcid":false,"given":"Hermelinda","family":"Salgado-Ceballos","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Neurol\u00f3gicas, Hospital de Especialidades Dr. Bernardo Sep\u00falveda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia J.","family":"Segura-Uribe","sequence":"additional","affiliation":[{"name":"Departamento de Investigaci\u00f3n Traslacional en Farmacoepidemiolog\u00eda, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4880-8597","authenticated-orcid":false,"given":"Julio","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Neurociencias, Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Guerra-Araiza","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, Hospital de Especialidades Dr. Bernardo Sep\u00falveda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica","family":"Coyoy-Salgado","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, Hospital de Especialidades Dr. Bernardo Sep\u00falveda, Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.4103\/1673-5374.385849","article-title":"The secondary injury cascade after spinal cord injury: An analysis of local cytokine\/chemokine regulation","volume":"19","author":"Hellenbrand","year":"2024","journal-title":"Neural Regen. 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