title: Positive association between blood brain barrier disruption and osmotically-induced demyelination.
abstract: Rapid correction of chronic hyponatremia can cause osmotic brain demyelination in animals and humans. Why demyelination develops is unknown, but blood brain-barrier disruption might expose oligodendrocytes to substances normally excluded from the brain. To test this hypothesis, chronic hyponatremia was induced and corrected using a new, reproducible rat model for producing osmotic brain demyelination. Blood brain barrier integrity was assessed by NMR imaging at either 3, 16 or 24 h during the first day of correction. Demyelination was determined histopathologically 5 - 6 days later. Of 96 rats studied, demyelination developed 5 - 6 days later in 37 rats, 89% of whom showed barrier disruption. In the 59 rats who did not develop demyelination, 45 (76%) had no barrier disruption. Thus, blood-brain barrier disruption during the first 24 h of correction was associated with a 70% risk of developing demyelination. By contrast, the risk of developing subsequent demyelination was only 8% when the barrier was intact. This strong association between barrier disruption and subsequent demyelination provides new insights into the role of blood brain barrier function in demyelinative disorders such as the osmotic demyelination syndrome and by extension to other demyelinative disorders such as multiple sclerosis.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, 937 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15216, USA.
authors.forename: S
authors.initials: S
authors.lastname: Adler
authors.forename: J
authors.initials: J
authors.lastname: Martinez
authors.forename: D S
authors.initials: DS
authors.lastname: Williams
authors.forename: J G
authors.initials: JG
authors.lastname: Verbalis
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects; D003711:Demyelinating Diseases / Q000503:physiopathology*; D004195:Disease Models, Animal; D006982:Hypertonic Solutions / Q000494:pharmacology; D007010:Hyponatremia / Q000188:drug therapy / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D006982:Hypertonic Solutions; D012964:Sodium