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.

低钠血症是临床上最常见的病症之一 药品。 该项目的主要目标是研究对 大脑对急性和慢性低钠血症的适应，以及 大脑对纠正低钠血症的反应。 我们已经在一个 血浆钠浓度快速增加的大鼠模型或 血浆渗透压会破坏血脑屏障（BBB）；那个这个 慢性低钠血症患者血浆渗透压较低时会发生破坏 与正常血压对照大鼠相比；血浆迅速增加 钠和血浆渗透压导致全球显着增加 低钠血症和正常钠血症大鼠的脑灌注；和 BBB 的破坏似乎与随后的 脑脱髓鞘的发展。 今年我们评估了效果 DPSPX（一种腺苷 1 和 2 受体阻滞剂）对渗透压诱导的影响 脑灌注增加。 八只大鼠接受 DPSPX 静脉注射高渗钠之前。 DPSPX 没有 防止脑灌注增加表明腺苷 可能不参与脑灌注的改变 由 CHN 的快速校正引起。 我们未来的实验将集中于 血脑屏障通透性的改变和大脑的变化 血浆渗透压快速变化后的灌注与 神经系统症状和大脑的后续发展 脱髓鞘通常发生在低钠血症快速纠正之后。 具体来说，我们希望确定（i）负责的机制 渗透压诱导的脑灌注增加，并确定 灌注的这种变化是否以及如何影响渗透破坏 大脑的发育和随后脱髓鞘的发展 快速纠正低钠血症，(ii) 负责调节的介质 纠正低钠血症期间脑灌注的变化， (iii) 确定渗透作用的机制 血脑屏障的开放以及这可能如何导致随后的脱髓鞘。