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

Abstract

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.

Astrocytes Are an Early Target in Osmotic Demyelination Syndrome

“…39,51 Together, these observations provide several mechanistic links between astrocyte death and the ensuing demyelination seen in ODS.…”

“…38 Rapid recognition of ODS could aid in treatment because prompt reduction in serum sodium levels can benefit patients in the early stages of the disease. 39,40 Therefore, we investigated whether the early neurologic manifestations and fatal outcome in ODS could be predicted on the basis of serum S100B levels. Compared with asymptomatic rats, we showed that 24 hours after serum sodium correction, S100B was significantly higher in rats undergoing early neurologic manifestations (within 2 days postcorrection).…”

“…Rats were allowed to eat 1 day after the correction and drink 2 days after the correction to avoid a secondary decrease in serum sodium levels. 39 Procedures were performed in accordance with the guidelines for animal care at Université Libre de Bruxelles.…”

Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia

“…We successfully used a previously described model ( Figure 1) 5,6,18 to induce chronic severe hyponatremia in all rats. In these experiments, only rats who had severe hyponatremia (SNa Ͻ 120 mEq/L) were included in the analysis.…”

“…The physiopathology of this disorder is not yet fully understood, and an experimental murine model has been developed to better understand the mechanisms leading to myelin damage after an osmotic injury. 2,5,6 Previous experiments have suggested that ODS might share key characteristics with other models of central nervous system demyelination in which both opening of the blood-brain barrier (BBB) and microglia-macrophage activation are involved in the genesis of demyelinative changes. [7][8][9][10][11] Minocycline is a second-generation tetracycline that has been well studied in various models of brain pathology including autoimmune or ischemic myelin damage, and others have reported that administration of minocycline in CNS injury was associated with a striking reduction in BBB permeability, inhibition of microglia-macrophage activation, and inflammatory cytokines secretion, with subsequent benefits in mortality and functional outcome.…”