CORRECTION OF HYPONATREMIA & PATHOGENESIS OF OSMOTIC INDUCED DEMYELINATION

纠正低钠血症

• 批准号: 6121738
• 负责人: SHELDON ADLER
• 金额: $ 9.82万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121738
• 关键词: Mammalia; biomedical resource; magnetic resonance imaging; nervous system

Hyponatremia is among the most comon conditions found in clinical medicine. The main goal of this project is to study the effect on the brain of the adaptation to acute and chronic hyponatremia, and the brain's response to correction of hyponatremia. We have shown in a rat model that rapid increases in plasma sodium concentration or plasma osmolality can disrupt the blood-brain barrier (BBB); that this disruption occurs at a lower plasma osmolality in chronic hyponatremic rats than in normonatremic controls; that a rapid increase in plasma sodium and plasma osmolality causes a marked global increase in cerebral perfusion in both hyponatremic and normonatremic rats; and that disruption of BBB appears to be related to the subsequent development of brain demylenation. This year we assessed the effect of DPSPX, an adenosine ~ and 2 receptor blocker on osmolar induced increases in cerebral perfusion. Eight rats were administered DPSPX prior to receiving hypertonic sodium intravenously. DPSPX did not prevent the increase in cerebral perfusion showing that adenosine probably is not involved in the alterations in cerebral perfusion induced by rapid correction of CHN. Our future experiments will focus on how alterations in BBB permeability and the changes in cerebral perfusion which follow rapid changes in plasma osmolality relate to the subsequent development of neurologic symptoms and brain demylenation which often follow rapid correction of hyponatremia. Specifically, we hope to identify (i) the mechanisms responsible for the osmolar induced increase in cerebral perfusion, and to determine whether and how such changes in perfusion influence osmotic disruption of the brain and subsequent development of demylenation following rapid correction of hyponatremia, (ii) the mediators responsible for the changes in cerebral perfusion during correction ofhyponatremia, and (iii) to identify the mechanisms responsible for the osmotic opening of the BBB and how this might cause subsequent demylenation.

低钠血症是临床中发现的最COMON的疾病之一 药品。 该项目的主要目标是研究对 适应急性和慢性低钠血症的大脑，以及 大脑对低钠血症纠正的反应。 我们已经显示了 大鼠模型快速增加血浆钠浓度或 血浆渗透气可以破坏血脑屏障（BBB）；那 破坏发生在慢性低钠症的较低血浆渗透压下 大鼠比正常流血对照中的大鼠；血浆迅速增加 钠和血浆渗透压导致全球明显增加 低钠血症和正常钠大鼠的脑灌注；和 BBB的破坏似乎与后续 大脑范围的发展。 今年我们评估了效果 DPSPX，渗透诱导的腺苷〜和2受体阻滞剂 脑灌注的增加。 八只大鼠DPSPX 在静脉内接受高渗钠之前。 DPSPX没有 防止脑灌注的增加表明腺苷 可能不参与大脑灌注的改变 通过快速校正CHN诱导。 我们未来的实验将集中精力 关于BBB渗透性的变化和脑的变化如何 血浆渗透压快速变化的灌注与 随后的神经系统症状和大脑的发展 经常遵循低钠血症快速纠正的降低化。 具体来说，我们希望确定（i）负责的机制 渗透诱导的脑灌注增加，并确定 灌注中这种变化是否影响渗透性破坏 大脑和随后的销售发展之后的发展 低钠血症的快速纠正，（ii）负责的介体 矫正期间血症中脑灌注的变化， （iii）确定负责渗透的机制 BBB的开放及其如何导致随后的降低。