TRAINING & DISSEMINATION

低钠血症是临床上最常见的情况之一。 医药。这个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 血浆钠浓度快速升高的大鼠模型 血浆渗透压可破坏血脑屏障；这 慢性低钠血症患者在较低的血浆渗透压时发生紊乱 比正常血压对照组大鼠；血浆迅速增加 钠和血浆渗透压导致全球范围内 低钠血症大鼠和正常钠血症大鼠的脑血流灌注； 血脑屏障的中断似乎与随后的 大脑脱髓鞘的发展。今年，我们评估了这种影响 腺苷和2受体阻断剂DPSPX对渗透压的影响 大脑灌注量增加。给8只大鼠注射DPSPX 在静脉注射高渗钠之前。DPSPX没有 防止脑血流灌注量的增加显示腺苷 可能与脑血流灌注的改变无关 由CHN快速矫正所致。我们未来的实验将集中在 血脑屏障通透性改变与脑组织改变的关系 血浆渗透压快速变化后的血流灌注与 神经症状和脑的后续发展 通常伴随着低钠血症的快速纠正而出现的脱膜现象。 具体地说，我们希望确定(一)负责 渗透压诱导的脑血流灌注增加，并确定 这种血流灌注的变化是否以及如何影响渗透紊乱 大脑和随后的去膜化的发展 迅速纠正低钠血症，(Ii)负责 纠正低钠血症时脑血流灌注的变化 以及(Iii)确定导致渗透的机制 BBB的开放，以及这可能如何导致随后的去货币化。

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.