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Anstalt \u00f6ffentlichen Rechts"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Cladribine is a synthetic purine analogue that interferes with DNA synthesis and repair next to disrupting cellular proliferation in actively dividing lymphocytes. The compound is approved for the treatment of multiple sclerosis (MS). Cladribine can cross the blood\u2013brain barrier, suggesting a potential effect on central nervous system (CNS) resident cells. Here, we explored compartment-specific immunosuppressive as well as potential direct neuroprotective effects of oral cladribine treatment in experimental autoimmune encephalomyelitis (EAE) mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In the current study, we compare immune cell frequencies and phenotypes in the periphery and CNS of EAE mice with distinct grey and white matter lesions (combined active and focal EAE) either orally treated with cladribine or vehicle, using flow cytometry. To evaluate potential direct neuroprotective effects, we assessed the integrity of the primary auditory cortex neuronal network by studying neuronal activity and spontaneous synaptic activity with electrophysiological techniques ex vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Oral cladribine treatment significantly attenuated clinical deficits in EAE mice. Ex vivo flow cytometry showed that cladribine administration led to peripheral immune cell depletion in a compartment-specific manner and reduced immune cell infiltration into the CNS. Histological evaluations revealed no significant differences for inflammatory lesion load following cladribine treatment compared to vehicle control. Single cell electrophysiology in acute brain slices was performed and showed an impact of cladribine treatment on intrinsic cellular firing patterns and spontaneous synaptic transmission in neurons of the primary auditory cortex. Here, cladribine administration in vivo partially restored cortical neuronal network function, reducing action potential firing. Both, the effect on immune cells and neuronal activity were transient.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results indicate that cladribine exerts a neuroprotective effect after crossing the blood\u2013brain barrier independently of its peripheral immunosuppressant action.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-022-02588-7","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T06:02:36Z","timestamp":1667887356000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cladribine treatment improves cortical network functionality in a mouse model of autoimmune encephalomyelitis"],"prefix":"10.1186","volume":"19","author":[{"given":"Christina B.","family":"Schroeter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leoni","family":"Rolfes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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All patients included in this study gave their written informed consent in accordance with the Declaration of Helsinki and a protocol approved by the Ethics Committee of the University of Duesseldorf\u00a0(5951R).\u00a0","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors qualify for authorship according to current guidelines of <i>Journal of Neuroinflammation<\/i>. All authors have read and agreed to the submitted version of the manuscript. The current manuscript is not submitted to or under revision at another journal. The submitting author hereby declares that she takes responsibility for conduction and analysis of the data and that he had full access to all study data. The submitting author furthermore declares that there are no competing interests concerning these data and that the authors have all rights to publish the data. The submitted manuscript does not contain data that have been published in any other journal. The authors have no related articles under submission.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Christina B. Schroeter: None. Leoni Rolfes: received travel reimbursements from Merck Serono and Sanofi Genzyme, research support from Diamed, Merck Serono and Novartis. Her research is funded by the Interdisciplinary Center for Clinical Studies (IZKF) Muenster. K. S. Sophie Gothan: None. Joel Gruchot: None. Alexander M. Herrmann: None. Stefanie Bock: None. Luca Fazio: None. Antonia Henes: None. Venu Narayanan: None. Steffen Pfeuffer: received travel grants from Sanofi Genzyme and Merck Serono, lecturing honoraria from Sanofi Genzyme, Mylan Healthcare, and Biogen, and research support from Diamed, Merck Serono, and the German Multiple Sclerosis Society Northrhine-Westphalia. Christopher Nelke: None. Saskia R\u00e4uber: None. Niklas Huntemann: None. Eduardo Duarte-Silva: None. Vera Dobelmann: None. Petra Hundehege: None. Heinz Wiendl: None. Katharina Raba: None. Patrick K\u00fcry: None. David Kremer: None. Tobias Ruck: received travel expenses and financial research support from Genzyme and Novartis and received honoraria for lecturing from Roche, Merck, Genzyme, Biogen, and Teva. Thomas M\u00fcntefering: None. Thomas Budde: received research funding from Biogen, DFG and IZKF M\u00fcnster. Manuela Cerina: None. Sven G. Meuth: received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Else Kr\u00f6ner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology, and by Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche, and Teva.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"270"}}