PREVENTION OF BRAIN DEMYELINATION IN RATS AFTER EXCESSIVE CORRECTION OF CHRONIC HYPONATREMIA BY SERUM SODIUM LOWERING

Brain myelinolysis occurs after correction of chronic hyponatremia in rats when the magnitude of increase in serum sodium (DELTAS(Na)) excee ds 20 to 25 mEq/liter/24 hr (the critical threshold for brain). We tes ted the hypothesis that after a sustained excessive correction, brain lesions (BL) could be prevented by subsequently decreasing the serum s odium below the critical threshold for brain through the administratio n of hypotonic fluids. After three days of severe (< 115 mEq/liter) ch ronic (3 days) hyponatremia, 55 rats were submitted to an excessive co rrection (DELTAS(Na) > 25 mEq/liter) by a single i.p. infusion of hype rtonic saline (NaCl). This osmotic stress was maintained during 12 hou rs before the serum sodium decrease was initiated. Thirty-two rats rea ched the twelfth post-correction hour without symptoms. In group 1 aft er a large (DELTAS(Na) 32 mEq/liter) and sustained (12 hr) osmotic str ess, the natremia was rapidly (2 hr) decreased by the administration o f oral tap water and, at the end of the first 24 hours, the magnitude of correction was maintained below 20 mEq/liter/24 hr. All the rats fa red well in this group and were free of neurologic symptoms. Mild BL w ere noticed in only 20% of them. On the contrary, in controls (no hypo tonic fluids administration at the twelfth hour) whose serum sodium wa s left overcorrected, all the rats became symptomatic and 57% of them died rapidly. Brain damage developed in 100% of the surviving rats. In group 2, despite hypotonic fluids administration, the serum sodium de creased insufficiently and the correction was > 20 mEq/liter at the en d of the first 24 hours (DELTAS(Na) 25 mEq/liter). The majority of the se rats also presented a poor outcome. Finally, a group of rats develo ped very early (< 12 hr) neurologic symptoms (N = 23, 42%), and all of them died rapidly (< 24 hr) if the natremia was not decreased. Hypoto nic fluids administration in some of these rats allowed them a longer survival, and brain analysis also demonstrated severe demyelination. T his work demonstrates that the process leading to brain demyelination remains reversible in hyponatremic rats despite a sustained (12 hr) ex posure to an excessive correction. Indeed, subsequent brain damage can be completely prevented in asymptomatic rats by early (12 hr) serum s odium lowering provided that the final correction was maintained below 20 mEq/liter/24 hr. Our results also show that the osmotic stress mus t be maintained a minimum period of time to induce brain lesions.