Re-induction of hyponatremia after rapid overcorrection of hyponatremia reduces mortality in rats

Kidney Int. 2009 Sep;76(6):614-21. doi: 10.1038/ki.2009.254. Epub 2009 Jul 15.


Osmotic demyelination syndrome is a devastating neurologic disorder often seen after the rapid correction of chronic hyponatremia. The permeability of the blood-brain barrier is increased in experimental osmotic demyelination, and some have suggested that corticosteroids protect against this disorder by keeping the permeability of the blood-brain barrier low. We previously reported that re-lowering of the serum sodium after rapid correction of chronic hyponatremia was beneficial if performed early in the course (12 to 24 h). Here we compared mortality, blood-brain barrier permeability, and microglial activation in rats after the rapid correction of chronic hyponatremia. We studied three groups of rats after correction of chronic hyponatremia: and treated them with sodium chloride, with or without dexamethasone; or with sodium chloride followed by re-induction of hyponatremia. We found that treatment with dexamethasone or re-induction of hyponatremia effectively prevented the opening of the blood-brain barrier, reduced neurological manifestations, and decreased microglial activation; however, only re-induction of hyponatremia resulted in a significant decrease in mortality 5 days after the correction of chronic hyponatremia. Restoring the permeability of the blood-brain barrier to normal levels did not decrease mortality. Our results suggest that after inadvertent rapid correction of hyponatremia, treatment options should favor re-lowering serum sodium. The increased permeability of blood-brain barrier seen in osmotic demyelination syndrome may not be a primary pathophysiologic insult of this syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Dexamethasone / therapeutic use
  • Hyponatremia / complications
  • Hyponatremia / mortality
  • Hyponatremia / therapy*
  • Immunoglobulin G / analysis
  • Male
  • Myelinolysis, Central Pontine / etiology*
  • Myelinolysis, Central Pontine / physiopathology
  • Myelinolysis, Central Pontine / therapy
  • Osmotic Pressure
  • Permeability
  • Rats
  • Rats, Wistar
  • Sodium / blood


  • Immunoglobulin G
  • Dexamethasone
  • Sodium