{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:26:18Z","timestamp":1788981978303,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Spanish Government","award":["Red TerCel ISCIII RD12\/0019\/0033"],"award-info":[{"award-number":["Red TerCel ISCIII RD12\/0019\/0033"]}]},{"name":"Spanish Government","award":["PI12\/02574-ISCIII"],"award-info":[{"award-number":["PI12\/02574-ISCIII"]}]},{"name":"Spanish Government","award":["RD16\/0011\/0025"],"award-info":[{"award-number":["RD16\/0011\/0025"]}]},{"name":"Spanish Government","award":["RTC-2015-3309-1"],"award-info":[{"award-number":["RTC-2015-3309-1"]}]},{"name":"Andalusian Government","award":["Excellence project-P12-CTS-2739"],"award-info":[{"award-number":["Excellence project-P12-CTS-2739"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The use of long\u2010term immunosuppressive treatments on neural transplantation has been controversial during the last decades. Although nowadays there is a consensus about the necessity of maintaining a permanent state of immunosuppression to preserve the survival of cerebral grafts, little is known about the effects that chronic immunosuppression produces both on the neurodegenerative process and on transplants function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we establish a new immunosuppressive protocol, based on the discontinuous administration of CsA (15\u00a0mg\/kg; s.c.) and prednisone (20\u00a0mg\/kg; s.c.), to produce long\u2010term immunosuppression in mice. Using this treatment, we analyse the effects that long\u2010term immunosuppression induces in a chronic 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6,\u2010tetrahydropyridine (<jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>) model of parkinsonism and on the neuroprotective and neurorestorative anti\u2010parkinsonian actions exerted by rat carotid body (<jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>) xenografts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This protocol preserves the survival of rat <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content> xenotransplants maintaining the general wellness of the grafted mice. Although permanent immunosuppression does not prevent the <jats:styled-content style=\"fixed-case\">MPTP<\/jats:styled-content>\u2010induced cell death of nigral neurons and the consequent degeneration of dopaminergic striatal innervation, allowing for its use as Parkinson's disease (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) model, it reduces the microglial activation and slightly declines the striatal damage. Moreover, we reported that chronic administration of immunosuppressant drugs does not alter the neuroprotective and restorative anti\u2010parkinsonian actions of rat <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content> xenografts into parkinsonian mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This new immunosuppressive protocol provides a new murine model to assay the long\u2010term effects of cerebral xenografts and offer a pharmacological alternative to the commonly used genetic immunodeficient mice, allowing the use of genetically modified mice as hosts. In addition, it will permit the experimental analysis of the effects produced by human <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content> xenografts in the chronic <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> murine model, with the final aim of using <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content> allografts as an option of cell therapy in <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12410","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T09:31:27Z","timestamp":1529659887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Long\u2010term immunosuppression for <scp>CNS<\/scp> mouse xenotransplantation: Effects on nigrostriatal neurodegeneration and neuroprotective carotid body cell therapy"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-9013","authenticated-orcid":false,"given":"Javier","family":"Villadiego","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla\u2010IBiS Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla  Sevilla Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Romo\u2010Madero","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla\u2010IBiS Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Garc\u00eda\u2010Swinburn","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla\u2010IBiS Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nela","family":"Su\u00e1rez\u2010Luna","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla\u2010IBiS Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Bermejo\u2010Navas","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla\u2010IBiS Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Echevarr\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla\u2010IBiS Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7512-7135","authenticated-orcid":false,"given":"Juan J.","family":"Toledo\u2010Aral","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla\u2010IBiS Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica Universidad de Sevilla  Sevilla Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810083391506"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810153391607"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.13"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2165"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/399a032"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25378"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.123"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2105529"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199211263272202"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199211263272203"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/16060"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.4749"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103083441002"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10720"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(88)90069-X"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80449-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80733-3"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-01-00141.2003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.06.001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4312-04.2005"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000073315.88827.72"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.106021"},{"key":"e_1_2_9_25_1","first-page":"13","article-title":"CD4+ T cells mediate cytotoxicity in neurodegenerative diseases","volume":"119","author":"Appel SH","year":"2009","journal-title":"J Clin Invest"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70062-6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8052-0"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00686-5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-3019(96)00190-5"},{"key":"e_1_2_9_30_1","first-page":"1","article-title":"Cyclosporin promotes neurorestoration and cell replacement therapy in pre\u2010clinical models of Parkinson's disease","volume":"9","author":"Tamburrino A","year":"2015","journal-title":"Acta Neuropathol Commun"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5983-09.2010"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413201111"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu377"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.01.014"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1308"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000066"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.05.027"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13409"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1002\/9780470751077","volume-title":"Handbook of Laboratory Animal Management and Welfare","author":"Wolfensohn S","year":"2003"},{"key":"e_1_2_9_40_1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos G","year":"1997"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(93)90112-O"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.19.8935"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2818.1997.2070765.x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1987.tb02837.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2818.1999.00457.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0122-06.2006"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00237035"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2008.10.001"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.38.8.1285"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410380307"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.08.031"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368914X678526"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13704"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000166"},{"key":"e_1_2_9_55_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/BF00271860","article-title":"Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug\u2010induced behaviour, and dopamine release","volume":"70","author":"Brundin P","year":"1988","journal-title":"Exp Brain Res"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90338-7"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7738"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368916X691682"},{"key":"e_1_2_9_59_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF00271854","article-title":"Xenografting of fetal mouse hippocampal tissue to the brain of adult rats: effects of cyclosporin A treatment","volume":"70","author":"Finsen B","year":"1988","journal-title":"Exp Brain Res"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2012.05.003"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2004.01.013"},{"key":"e_1_2_9_62_1","first-page":"493","article-title":"Cyclosporine in transplantation \u2010 a history of converging timelines","volume":"25","author":"Colombo D","year":"2011","journal-title":"J Biol Regul Homeost Agents"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00229996"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)83014-4"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970601)48:5<385::AID-JNR1>3.0.CO;2-A"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00790-2"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.6.1121"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(02)00938-1"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02715.x"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.2217\/rme.12.22"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-009-0201-5"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1937-6448(08)01001-0"}],"container-title":["Xenotransplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fxen.12410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/xen.12410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T21:38:03Z","timestamp":1694813883000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/xen.12410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,22]]},"references-count":71,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/xen.12410"],"URL":"https:\/\/doi.org\/10.1111\/xen.12410","archive":["Portico"],"relation":{},"ISSN":["0908-665X","1399-3089"],"issn-type":[{"value":"0908-665X","type":"print"},{"value":"1399-3089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,22]]},"assertion":[{"value":"2018-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12410"}}