title: Astrocytes are an early target in osmotic demyelination syndrome.
abstract: Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.
authors: Erasme University Hospital, Department of General Internal Medicine, Research Unit on Hydromineral Metabolism, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. fgankamk@ulb.ac.be
authors: Fabrice
authors: F
authors: Gankam Kengne
authors: Charles
authors: C
authors: Nicaise
authors: Alain
authors: A
authors: Soupart
authors: Alain
authors: A
authors: Boom
authors: Johan
authors: J
authors: Schiettecatte
authors: Roland
authors: R
authors: Pochet
authors: Jean Pierre
authors: JP
authors: Brion
authors: Guy
authors: G
authors: Decaux
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D017630:Connexins / Q000378:metabolism; D003711:Demyelinating Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation; D006984:Hypertrophy / Q000139:chemically induced; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D017628:Microglia / Q000187:drug effects; D009186:Myelin Sheath / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009997:Osmotic Pressure; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000009:adverse effects*; D012964:Sodium / Q000097:blood
chemical_list: D017630:Connexins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D012462:Saline Solution, Hypertonic; D012964:Sodium