Erasme University Hospital, Department of General Internal Medicine, Research Unit on Hydromineral Metabolism, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
J Am Soc Nephrol. 2011 Oct;22(10):1834-45. doi: 10.1681/ASN.2010111127. Epub 2011 Sep 1.
Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.
在慢性低钠血症的快速纠正过程中，渗透压的突然变化会导致脱髓鞘脑损伤，但快速渗透压变化与髓鞘丢失之间的事件序列尚不清楚。在这里，在渗透性脱髓鞘综合征的大鼠模型中，我们发现低钠血症快速纠正后会发生大量星形胶质细胞死亡，从而描绘出未来髓鞘丢失的区域。星形胶质细胞死亡导致星形胶质细胞-少突胶质细胞网络破裂，迅速上调炎症细胞因子基因，并增加血清 S100B，这可预测渗透性脱髓鞘的临床表现和结局。这些结果支持渗透压性脑损伤的病理生理学模型，其中低钠血症的快速纠正会引发星形胶质细胞凋亡，随后星形胶质细胞和少突胶质细胞之间的营养通讯丧失、继发炎症、小胶质细胞激活，最终导致脱髓鞘。
