Reinduction of hyponatremia improves survival in rats with myelinolysis-related neurologic symptoms

Brain myelinolysis occurs after excessive correction (Delta SNa > 20 mEq/1/24 hours) of chronic hyponatremia. However, we showed recently that the mechanisms leading to brain myelinolysis remain reversible. Indeed, reinduction of the hyponatremia by water administration despite 12 hours of sustained excessive correction could prevent the development of demyelination in rats still asymptomatic at that time. Whether this therapeutic maneuver could be also beneficial to rats with preexisting myelinolysis-related neurologic symptoms is unknown. Therefore we evaluated here the effect of reinduction of the hyponatremia on the survival and on brain damage in rats presenting obvious neurologic symptoms after excessive correction of hyponatremia. After 3 days of severe hyponatremia induced by 2.5 D-glucose in water and continuous infusion of AVP, rats were submitted to a large correction (Delta SNa similar to 30 mEq/l) by 2 i.p. injections of hypertonic saline given over 24 hours. In group I (n = 15) the rats developing neurologic symptoms during the first 24 hours of correction received one i.p. injection of distilled water which rapidly decreased the natremia to a final correction gradient < 20 mEq/1/24 hour. In group II (n = 13, controls) the symptomatic rats were left permanently overcorrected. In group I, after water administration, the neurological manifestations were generally attenuated or disappeared. Seven of the 15 rats (47%) in this group survived up to day 10 with a mean survival time of 7.5 +/- 2 days, an outcome clearly improved as compared to group TT (controls): only 1 of the 13 rats (7%, p < 0.03) was still alive on day 10 and the mean survival time was 3.3 +/- 2 days (p < 0.001) in this group II. The duration of the symptoms also influences the prognosis. In group I, in 9 rats the water administration was performed 4 hours after symptoms onset. These rats had a better outcome than the 6 rats with more sustained (8-10 hours) neurologic symptoms before water loading. Brain analysis in the 7 surviving rats of group I demonstrated demyelinating lesions in only 2 of them, suggesting the reversibility of the process even when neurologic manifestation developed. In conclusion, after exposure to an excessive correction of chronic hyponatremia, even when rats have developed myelinolysis-related neurologic symptoms, hypotonic fluids administration could improve survival and could prevent the subsequent development of brain myelinolysis.