Neuronal distress induced by low extracellular sodium in vitro is partially reverted by the return to normal sodium. 
Hyponatremia is associated with negative clinical outcomes even when chronic and mild.  It is also known that hyponatremia treatment should be appropriately performed, to avoid dramatic consequences possibly leading to death.  We have previously demonstrated that chronically low extracellular [Na(+)], independently of reduced osmolality, is associated with signs of neuronal cell distress, possibly involving oxidative stress.  The aim of the present study was to assess whether the return to normal extracellular [Na(+)] is able to revert neuronal cell damage.  After exposing SH-SY5Y and SK-N-AS cells to low [Na(+)] and returning to normal [Na(+)], we analyzed cell viability by MTS assay, ROS accumulation by FASCan and expression of anti-apoptotic genes.  We found that the viability of cells was restored upon return to normal [Na(+)].  However, when more subtle signs of cell distress were assessed, such as the expression level of the anti-apoptotic genes Bcl-2 and DHCR24 or of the heme oxygenase 1 gene, a complete return to basal values was not observed, in particular in SK-N-AS, even when [Na(+)] was gradually increased.  We also demonstrated that the amount of ROS significantly increased in low [Na(+)], thus confirming that oxidative stress appears to contribute to the effects of low [Na(+)] on cell homeostasis.  Overall, this study provided the first demonstration that the correction of chronically low extracellular [Na(+)] may not be able to revert all the cell alterations associated with reduced [Na(+)].  These results suggest that prompt hyponatremia treatment might prevent possible residual abnormalities.