CONTRAST MEDIA REDUCE CSF PRODUCTION MECHANISM/TOXICITY

造影剂不良反应的原因尚不清楚 了解但可能涉及CM引起的中枢神经改变 系统(CNS)。血脑屏障(BBB)严格控制 中枢神经系统的物质。脑脊液(CSF)产生率为 从中枢神经系统中消除物质的一个关键因素。这两个因素 从而维持和控制中枢神经系统的化学环境。如果有任何一个 因子被打乱，可能会出现中毒表现。这两个因素都可以是 由CM更改。造影剂的毒性高达几百倍 在中枢神经系统，并能够破坏血脑屏障。实验 在狗身上的实验表明，中等剂量的离子和 非离子静脉注射CM可显著减少脑脊液的产生。因此， CM可能会改变中枢神经系统的环境，并导致 毒性。CM对脑脊液产生影响的机制如下 在拟议的工作中进行了研究。清醒和麻醉的实验动物 将使用模型和体外制剂来确定： CM诱导脑脊液分泌减少的机制；中枢神经系统损害的程度 CM的这种作用产生的毒性；浓度的变化， CM引起的物质在中枢神经系统中的滞留和动力学； 通过额外降低CM毒性的某些危险因素 脑脊液的产生或使血脑屏障易于受到CM的破坏性影响；以及如果 从药理上保护CM的这些作用是可能的。

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.