TRAINING & DISSEMINATION

低钠血症是临床上最常见的疾病之一 药 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， 大脑对纠正低钠血症的反应 我们在一个 血浆钠浓度快速增加的大鼠模型，或 血浆渗透压可以破坏血脑屏障（BBB）;这 在慢性低钠血症患者中， 与正常钠血症对照组相比， 钠和血浆渗透压摩尔浓度导致 低钠血症和正常钠血症大鼠的脑灌注;以及 BBB的破坏似乎与随后的 大脑脱髓鞘的发展。 今年我们评估了 DPSPX是腺苷~（2+）受体阻断剂， 脑灌注增加。 8只大鼠给予DPSPX 在静脉注射高渗钠之前 DPSPX没有 阻止脑灌注的增加，表明腺苷 可能与脑灌注的改变无关 由CHN的快速纠正引起。 我们未来的实验将集中在 血脑屏障通透性的改变和脑组织的变化 在血浆渗透压迅速变化后的灌注与 神经系统症状和大脑的后续发展 通常在快速纠正低钠血症后发生脱髓鞘。 具体而言，我们希望确定（i）负责 渗透压引起脑灌注增加，并确定 灌注的这种变化是否以及如何影响渗透破坏 以及随后的脱髓鞘发展 快速纠正低钠血症，（ii）负责的介质 纠正低钠血症过程中脑灌注的变化， 和（iii）确定负责渗透的机制 血脑屏障的开放以及这可能导致随后的脱髓鞘。

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.