BRAIN MYELINOLYSIS FOLLOWING HYPERNATREMIA IN RATS

Brain myelinolysis could develop after excessive correction (Delta SNa > 20-25 mEq/l/24 hour [h]) of chronic hyponatremia; however, this neu rological event is not recognized as a complication of hypernatremia w hen arising from a normonatremic baseline. Previous animal studies wer e unable to reproduce these brain lesions in hypernatremia after acute increase of serum sodium to moderately hypernatremic levels. We hypot hesize that to produce brain dehydration and myelinolysis from normona tremic baseline requires a more important osmotic gradient than when s tarting from hyponatremic state. Rapid and sustained hypernatremia (at least >6 to 12 h) was induced in male rats by i.p. administration of NaCl 2 M (3 injections at 6 h intervals). The NaCl doses were determin ed to define two groups of hypernatremic rats (moderate and severe hyp ernatremia) for further analysis of the neurological outcome. In group 1 (moderate hypernatremia, n = 26) 8 rats died early (<12 h) after th e beginning of the NaCl administration without specific neurologic man ifestations. All the surviving rats fared well and were asymptomatic a t time of death (day 8). They were submitted for at least 6 to 12 h to a serum sodium gradient of 28 +/- 6 mEq/l. Brain analysis was normal in all of them without brain demyelinating lesions. In group 2 (n = 51 ), 24 rats also died rapidly (<12 h). The surviving rats developed sev ere neurologic symptoms as typically encountered in hyponatremic rats with myelinolysis. The majority of them died before day 8. The hyperna tremic gradient in this group was significantly higher than rats in gr oup 1 that completely recovered (mean Delta SNa: 39 +/- 8 mEq/l, p < 0 .001). In the 7 surviving rats (mean Delta SNa: 33 +/- 3 mEq/l) brain analysis demonstrated severe demyelinating lesions similar to the hist ologic changes observed in hyponatremia-related myelinolysis. We demon strated for the first time that high and sustained levels of hypernatr emia could induce brain myelinolysis and that the osmotic gradient nec essary to produce brain lesions is higher for normonatremic than for h yponatremic rats.