Soupart A, Penninckx R, Namias B, Stenuit A, Perier O, Decaux G
Department of Internal Medicine, Erasmus University Hospital, Brussels, Belgium.
J Neuropathol Exp Neurol. 1996 Jan;55(1):106-13. doi: 10.1097/00005072-199601000-00011.
Brain myelinolysis could develop after excessive correction (delta SNa > 20-25 mEq/1/24 hour [h]) of chronic hyponatremia; however, this neurological event is not recognized as a complication of hypernatremia when arising from a normonatremic baseline. Previous animal studies were unable to reproduce these brain lesions in hypernatremia after acute increase of serum sodium to moderately hypernatremic levels. We hypothesize that to produce brain dehydration and myelinolysis from normonatremic baseline requires a more important osmotic gradient than when starting 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 determined to define two groups of hypernatremic rats (moderate and severe hypernatremia) for further analysis of the neurological outcome. In group 1 (moderate hypernatremia, n = 26) 8 rats died early (< 12 h) after the beginning of the NaCl administration without specific neurologic manifestations. All the surviving rats fared well and were asymptomatic at 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 severe neurologic symptoms as typically encountered in hyponatremic rats with myelinolysis. The majority of them died before day 8. The hypernatremic gradient in this group was significantly higher than rats in group 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 histologic changes observed in hyponatremia-related myelinolysis. We demonstrated for the first time that high and sustained levels of hypernatremia could induce brain myelinolysis and that the osmotic gradient necessary to produce brain lesions is higher for normonatremic than for hyponatremic rats.
慢性低钠血症过度纠正（血钠变化幅度>20 - 25 mEq/L/24小时）后可能发生脑髓鞘溶解；然而，当从正常血钠基线水平引发高钠血症时，这种神经学事件并不被视为高钠血症的并发症。以往的动物研究未能在血清钠急性升高至中度高钠血症水平后引发的高钠血症中重现这些脑损伤。我们推测，相较于从低钠血症状态开始，从正常血钠基线水平产生脑脱水和髓鞘溶解需要更显著的渗透梯度。通过腹腔注射2 M NaCl（每隔6小时注射3次）在雄性大鼠中诱导快速且持续的高钠血症（至少>6至12小时）。确定NaCl剂量以定义两组高钠血症大鼠（中度和重度高钠血症），以便进一步分析神经学结局。在第1组（中度高钠血症，n = 26）中，8只大鼠在开始注射NaCl后早期（<12小时）死亡，无特定神经学表现。所有存活大鼠情况良好，死亡时（第8天）无症状。它们在至少6至12小时内处于28±6 mEq/L的血钠梯度下。对它们全部进行的脑分析均正常，无脑脱髓鞘病变。在第2组（n = 51）中，24只大鼠也迅速死亡（<12小时）。存活大鼠出现了典型的低钠血症伴髓鞘溶解大鼠所具有的严重神经学症状。它们中的大多数在第8天前死亡。该组的高钠血症梯度显著高于完全恢复的第1组大鼠（平均血钠变化幅度：39±8 mEq/L，p<0.001）。在7只存活大鼠（平均血钠变化幅度：33±3 mEq/L）中，脑分析显示出严重的脱髓鞘病变，类似于在低钠血症相关髓鞘溶解中观察到的组织学变化。我们首次证明，高水平且持续的高钠血症可诱导脑髓鞘溶解，并且产生脑损伤所需的渗透梯度在正常血钠大鼠中高于低钠血症大鼠。
