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To better understand the mechanism underlying the different distribution pattern for cranial nerve lesions in these autoimmune neuroinflammatory diseases, we focused on the CNS\u2013PNS transition zone (TZ) of the trigeminal and cochlear nerves in a MOG-driven active EAE model. These nerves were found to exhibit unique arrangements of anatomical barrier layers including the arachnoid and glia limitans, which affected cerebrospinal fluid (CSF) tracer distribution as well as CCR2\n                    <jats:sup>+<\/jats:sup>\n                    immune cell infiltration. Our data demonstrated that CCR2\n                    <jats:sup>+<\/jats:sup>\n                    immune cells accumulate at the TZ on both CNS side and PNS side of the trigeminal nerve and cochlear nerve, which mirror the locations of cranial nerve pathology observed clinically in patients with inflammatory demyelinating disease. On the other hand, the optic and olfactory nerves, which both lack a TZ, did not exhibit restrictions in immune cell localization. Overall, our results reconcile with the hypothesis that the segment of the cranial nerve that is exposed to CSF flow is more susceptible to CCR2\n                    <jats:sup>+<\/jats:sup>\n                    immune cell infiltration.\n                  <\/jats:p>","DOI":"10.1007\/s00401-025-02896-1","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T09:10:05Z","timestamp":1750324205000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Role of CSF flow and meningeal barriers in the development of inflammatory lesions at the CNS\u2013PNS transition zone of cranial nerves in autoimmune demyelinating diseases"],"prefix":"10.1007","volume":"149","author":[{"given":"Li","family":"Xin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Nishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Madarasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Pleskac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela C.","family":"Ivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitaka","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Aleandri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Locatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Luciani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T.","family":"Proulx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"2896_CR1","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1136\/jnnp-2014-310206","volume":"87","author":"T Akaishi","year":"2016","unstructured":"Akaishi T, Sato DK, Nakashima I, Takeshita T, Takahashi T, Doi H et al (2016) MRI and retinal abnormalities in isolated optic neuritis with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies: a comparative study. 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Some of the MRI imaging data utilizing different MRI sequences from the current study from case 1 at acute phase have been published as a case report in Japanese language in J-STAGE on January 31, 2022,\n                      \n                      . The first author of this case report (Fumitaka Shimizu\n                      )\n                      is a co-author of the current study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All animal experiments were authorized by the Veterinary Office of the Canton of Bern (license BE 138\/2020), Switzerland and ethically conducted in accordance with the regulations of the Swiss Federal Welfare Act (TSchG).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Both participants have provided a written and signed consent for publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for this publication"}}],"article-number":"65"}}