{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:58:46Z","timestamp":1764050326761,"version":"3.45.0"},"reference-count":50,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009945","name":"Merck KGaA","doi-asserted-by":"crossref","award":["10.13039\/100009945"],"award-info":[{"award-number":["10.13039\/100009945"]}],"id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic neuroinflammatory and demyelinating disease that causes disability in patients. Cladribine is an oral treatment that is used in relapsing\u2013remitting and active secondary progressive MS. T and B lymphocytes are especially sensitive to cladribine, which are transiently depleted upon short treatment courses. However, cladribine crosses the blood\u2013brain barrier (BBB), supporting the hypothesis that cladribine may affect central nervous system (CNS)-resident cells. In this study, we used human primary cells and human cell lines to test the effect of cladribine, at therapeutic concentrations, on cells of the CNS. In these conditions, cladribine did not affect survival, proliferation and the capacity of producing cytokines of human microglial cells (HMC3 cell line) or primary human astrocytes but enhanced the production of oxygen reactive species in both cell types. The initial differentiation of primary human neuronal progenitor cells was impaired when continuously exposed to the maximum therapeutic concentration of cladribine, but not when lower concentrations were used. However, cladribine protected differentiated SH-SY5Y human neuroblastoma cell line from oxidative stress-related cell death. In conclusion, using different in vitro cell models, we demonstrate that cladribine maintains the normal function of CNS glia and protects neuronal cells from oxidative stress damage.<\/jats:p>","DOI":"10.3390\/ijms262311311","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"11311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cladribine Preserves Normal Central Nervous System Cellular Activity and Promotes Neuroprotection to Oxidative Stress Damage"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-9533","authenticated-orcid":false,"given":"Herena","family":"Eixarch","sequence":"first","affiliation":[{"name":"Servei de Neurologia, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d\u2019Hebron (VHIR), Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8524-3305","authenticated-orcid":false,"given":"Laura","family":"Calvo-Barreiro","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d\u2019Hebron (VHIR), Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7701-9346","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Fissolo","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d\u2019Hebron (VHIR), Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovaci\u00f3n y Universidades, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ursula","family":"Boschert","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, F135\/002, 64293 Darmstadt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-369X","authenticated-orcid":false,"given":"Arnau","family":"Hervera","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d\u2019Hebron (VHIR), Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, 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Catalunya (Cemcat), Institut de Recerca Vall d\u2019Hebron (VHIR), Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9949-5901","authenticated-orcid":false,"given":"Carmen","family":"Espejo","sequence":"additional","affiliation":[{"name":"Servei de Neurologia, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Institut de Recerca Vall d\u2019Hebron (VHIR), Hospital Universitari Vall d\u2019Hebron, 08035 Barcelona, Spain"},{"name":"Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovaci\u00f3n y Universidades, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.cell.2023.03.008","article-title":"Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting","volume":"186","author":"Charabati","year":"2023","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/WCO.0000000000001370","article-title":"Recent developments in multiple sclerosis neuropathology","volume":"38","author":"Stadelmann","year":"2025","journal-title":"Curr. 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