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To investigate the physiopathology of ODS <jats:italic>in vivo<\/jats:italic>, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24\u00a0hr post\u2010correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48\u00a0hr post\u2010correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood\u2013brain barrier (BBB) leakages. Expression levels of IL\u20101\u03b2, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24\u00a0hr post\u2010correction, and reached type D at 48\u00a0hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS.<\/jats:p>","DOI":"10.1002\/glia.23268","type":"journal-article","created":{"date-parts":[[2017,11,23]],"date-time":"2017-11-23T10:22:51Z","timestamp":1511432571000},"page":"606-622","source":"Crossref","is-referenced-by-count":41,"title":["Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood\u2013brain barrier disruption in a murine model of osmotic demyelination syndrome"],"prefix":"10.1002","volume":"66","author":[{"given":"Joanna","family":"Bouchat","sequence":"first","affiliation":[{"name":"URPhyM \u2013 NARILIS, Universit\u00e9 de Namur Namur Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Couturier","sequence":"additional","affiliation":[{"name":"Department of General Medicine Erasme Hospital, Universit\u00e9 Libre de Bruxelles Bruxelles Belgium"},{"name":"Laboratory of Histology, Neuroanatomy and Neuropathology Universit\u00e9 Libre de Bruxelles Bruxelles Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Marneffe","sequence":"additional","affiliation":[{"name":"URPhyM \u2013 NARILIS, Universit\u00e9 de Namur Namur Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Gankam\u2010Kengne","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Neuroanatomy and Neuropathology Universit\u00e9 Libre de Bruxelles Bruxelles Belgium"},{"name":"Department of Nephrology EpiCURA Ath Ath Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Balau","sequence":"additional","affiliation":[{"name":"URPhyM \u2013 NARILIS, Universit\u00e9 de Namur Namur Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"De Swert","sequence":"additional","affiliation":[{"name":"URPhyM \u2013 NARILIS, Universit\u00e9 de Namur Namur Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pierre","family":"Brion","sequence":"additional","affiliation":[{"name":"Laboratory of Histology, Neuroanatomy and Neuropathology Universit\u00e9 Libre de Bruxelles Bruxelles Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Poncelet","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy, Biomechanics and Organogenesis Universit\u00e9 Libre de Bruxelles Bruxelles Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Gilloteaux","sequence":"additional","affiliation":[{"name":"URPhyM \u2013 NARILIS, Universit\u00e9 de Namur Namur Belgium"},{"name":"Department of Anatomical Sciences St George's University School of Medicine, Newcastle upon Tyne  United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9372-1496","authenticated-orcid":false,"given":"Charles","family":"Nicaise","sequence":"additional","affiliation":[{"name":"URPhyM \u2013 NARILIS, Universit\u00e9 de Namur Namur Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurpsyc.1959.02340140020004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.8.5574"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2883"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22971"},{"key":"e_1_2_7_6_1","article-title":"Human astrocytes: Secretome profiles of cytokines and chemokines","volume":"9","author":"Choi S. 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