EFFECT OF HYPONATREMIA ON BRAIN PH FUNCTION MORPHOLOGY

低钠血症对脑 PH 功能形态的影响

• 批准号: 3412542
• 负责人: SHELDON ADLER
• 金额: $ 20.44万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-30 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3412542
• 关键词: acidity /alkalinity; brain circulation; brain disorders; brain metabolism; buffers; carbon dioxide tension; electrolyte balance; glucose metabolism; histopathology; hyponatremia; laboratory rat; membrane transport proteins; morphology; neurophysiology; nuclear magnetic resonance spectroscopy; osmotic pressure

DESCRIPTION: (Adapted from the Applicant's abstract): The general objective of the proposed 4-year series of animal investigations is to study the effect of hyponatremia, the most common electrolyte disorder in clinical medicine, on brain pH, brain function, and brain morphology. Hyponatremia is associated with many central nervous system (CNS) symptoms and lesions and its correction has been implicated in causing central pontine myelinolysis. The proposed studies in rats in both acute and chronic hyponatremia will determine the morphologic and functional CNS effects accompanying the adaptation to acute and chronic sustained hyponatremia, and the CNS effects occurring during its correction (deadaptation). Chronic, stable, non-catabolic hyponatremia will be produced in rats by constant subcutaneous DDAVP infusion. DDAVP will be administered via osmotic minipumps implanted subcutaneously in the back. Animals will be fed volume-limited liquid diets. In general, studies in these hyponatremia rats (1-14 days) will include: (1) 31P-NMR spectroscopy to measure resistance to changes in brain pH during acute metabolic acidosis; (2) intactness of the blood brain barrier using Gadolinium-DTPA contrast 1H-NMR imaging; (3) 31P-NMR in vivo spectroscopy to evaluate bioenergetics and brain buffering; the latter assessed by response to changes in CO2 tension; (4) phospholipid metabolism using high resolution 31P-NMR on brain extracts, (5) brain perfusion measured by trifluoromethane washout using 19F-NMR spectroscopy. Results will be compared to perfusion measurements made with 14C-iodoantipyrine; (6) regulation of brain buffering using specific inhibitors given into the cerebral ventricle; (7) brain water and electrolyte determination using standard methods; and, (8) brain histopathology. These methods will be used to study CNS effects of slow, moderate, and rapid correction of variable durations of hyponatremia. The effect of correcting hypoosmolality without altering sodium will be determined by giving mannitol IP and comparing results to isoosmolar correction of plasma sodium. Changes found in correction will be used to predict development of neurologic dysfunction and brain pathology. The knowledge obtained should lead to better understanding of the processes involved in adaptation to and correction of hyponatremia; better clinical management of this condition; and determination of whether hyponatremia is only a marker for increased morbidity and mortality or whether the condition makes the brain more susceptible to damage.

描述：（根据申请人的摘要进行了改编）：一般 拟议的4年动物调查系列的目的是 研究低钠血症的作用，这是最常见的电解质疾病 临床医学，脑pH，脑功能和脑形态。 低钠血症与许多中枢神经系统（CNS）症状有关 病变及其更正涉及引起中央 丘脑髓分解。 在急性和 慢性低钠血症将确定形态和功能性中枢神经系统 适应急性和慢性持续的效果 低钠血症和CNS校正期间发生的CNS效应 （Deadaptation）。 慢性，稳定，非代谢性低钠血症将是 通过恒定皮下DDAVP输注在大鼠中产生。 DDAVP将是 通过渗透微型木材皮下植入后部植入。 动物将被喂食容量有限的液体饮食。 通常，研究 这些低钠血症大鼠（1-14天）将包括：（1）31p-NMR光谱 测量急性代谢期间脑pH变化的抵抗力 酸中毒； （2）使用Gadolinium-DTPA完整的血脑屏障 对比1H-NMR成像； （3）31p-NMR体内光谱法进行评估 生物能学和大脑缓冲；后者通过对 二氧化碳张力的变化； （4）使用高分辨率的磷脂代谢 31P-NMR在脑提取物上，（5）通过三氟甲烷测量的脑灌注 使用19F-NMR光谱进行冲洗。 结果将与灌注进行比较 用14C-碘乙吡啶进行的测量； （6）大脑调节 使用给大脑心室的特定抑制剂缓冲； （7） 使用标准方法测定脑水和电解质；和（8） 大脑组织病理学。 这些方法将用于研究CNS的影响 缓慢，中度和快速校正低钠血症的持续时间。 在不改变钠的情况下纠正低弹性的效果将是 通过给出甘露醇IP并将结果与​​等值效果进行比较来确定 血浆钠的校正。 校正中发现的更改将用于 预测神经功能障碍和脑病理学的发展。 这 获得的知识应该可以更好地理解过程 参与对低钠血症的适应和矫正；更好的临床 管理这种情况；并确定低钠血症是否为 仅是提高发病率和死亡率的标记，或者是否 条件使大脑更容易受到损害。