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CONTRAST MEDIA REDUCE CSF PRODUCTION MECHANISM/TOXICITY

造影剂降低 CSF 产生机制/毒性

基本信息

批准号：
3179662
负责人：
Phillip Harnish
金额：
$ 11.17万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-30 至 1989-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3179662
关键词：
cerebrospinal fluid contrast media disease /disorder model drug adverse effect neuropharmacology toxin metabolism

项目摘要

The causes of the adverse responses to contrast media (CM) are not well understood but may involve CM-induced alterations of the central nervous system (CNS). The blood brain barrier (BBB) strictly controls access of substance to the CNS. The rate of cerebrospinal fluid (CSF) production is a key factor in eliminating substances from the CNS. These two factors thus maintain and control the chemical environment of the CNS. If either factor is disrupted, toxic manifestations could occur. Both factors can be altered by CM. Contrast media are up to several hundred times more toxic in the CNS than systemically, and are able to disrupt the BBB. Experiments in dogs from this laboratory show that moderate doses of both ionic and non-ionic intravenous CM substantially decrease CSF production. Therefore, CM might be expected to alter the environment of the CNS and result in toxicity. The mechanisms of CM effects on the production of CSF will be studied in the proposed work. Conscious and anesthetized laboratory animal models and in vitro preparations will be employed to determine: the mechanisms of CM-induced ecreased CSF production; the extent of CNS toxicity resulting from this action of CM; changes in the concentration, retention and kinetics of substances in the CNS caused by CM; enhancement by certain risk factors of CM-induced toxicity by additionally decreasing CSF production or by predisposing the BBB to damaging effects of CM; and if it is possible to protect from these effects of CM pharmacologically.

造影剂（CM）不良反应的原因尚不清楚已被理解，但可能涉及 CM 引起的中枢神经改变系统（中枢神经系统）。血脑屏障（BBB）严格控制其进入物质进入中枢神经系统。脑脊液（CSF）的产生率为消除中枢神经系统物质的关键因素。这两个因素从而维持和控制中枢神经系统的化学环境。如果其中之一因子被破坏，可能会出现毒性表现。这两个因素都可以由 CM 更改。造影剂的毒性高达数百倍在中枢神经系统中比系统性的更有效，并且能够扰乱血脑屏障。实验该实验室的狗实验表明，中等剂量的离子和非离子静脉注射 CM 显着降低脑脊液的产生。所以， CM 可能会改变中枢神经系统的环境并导致毒性。 CM 对 CSF 产生的影响机制如下：在拟议的工作中进行了研究。清醒且麻醉的实验动物模型和体外制剂将用于确定： CM 诱导脑脊液产生增加的机制；中枢神经系统的范围 CM 的这种作用产生的毒性；浓度的变化， CM 引起的中枢神经系统中物质的滞留和动力学；增强通过额外降低CM引起的毒性的某些危险因素 CSF 产生或使 BBB 易于受到 CM 的破坏性影响；如果从药理上来说，可以防止 CM 的这些影响。