title: Effect of rapid correction of hyponatremia on the blood-brain barrier of rats.
abstract: Brain demyelination sometimes follows rapid correction of hyponatremia, especially if the hyponatremia is chronic. During correction brain water decreases and the brain shrinks. The present study examined whether such shrinkage might be sufficient to disrupt the tight junctions of the blood-brain barrier. Barrier intactness was evaluated using magnetic resonance imaging and intravenous gadolinium contrast administration. Hypertonic saline infusion rapidly increased the plasma sodium concentration and caused barrier disruption more frequently in chronic than in acute hyponatremic rats. Similar increases in plasma sodium concentration did not disrupt the barrier in normonatremic rats. The disruption appeared to be due to altered plasma osmolality since infusion of hypertonic mannitol, which raised plasma osmolality without changing the plasma sodium concentration, disrupted the barrier in hyponatremic but not normonatremic rats. Moreover, the osmotic threshold for barrier disruption was lowest in chronic hyponatremia, intermediate in acute hyponatremia, and highest in normonatremia. The greater susceptibility to osmotic disruption in chronic hyponatremia suggests that blood-brain barrier disruption may play a significant role in causing the demyelination sometimes found following too rapid correction of hyponatremia, possibly through exposure of oligodendrocytes to plasma macromolecules such as complement.
authors.affiliation: Montefiore Renal W919, University of Pittsburgh School of Medicine, PA 15213-2582, USA.
authors.forename: S
authors.initials: S
authors.lastname: Adler
authors.forename: J G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: D
authors.initials: D
authors.lastname: Williams
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D007010:Hyponatremia / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D012462:Saline Solution, Hypertonic; D008353:Mannitol