A simple and rapid method to collect the cerebrospinal fluid of rats and its application for the assessment of drug penetration into the central nervous system
A simple and rapid method to collect the cerebrospinal fluid of rats and its application for the assessment of drug penetration into the central nervous system
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DOI：
10.1016/j.jneumeth.2008.12.001
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发表时间：
2009-03-30
影响因子：
3
通讯作者：
Benade, Vijay
中科院分区：
文献类型：
--
作者：
Nirogi, Ramakrishna;Kandikere, Vishwottam;Benade, Vijay
许多中枢神经系统（CNS）药物发现计划需要成功收集脑脊液（CSF），以评估CNS渗透和新化学实体的分布。本研究的目的是简化从大鼠枕大池收集最大量CSF的技术。将大鼠用5%氟烷麻醉并定位在立体定位框架中。大鼠头部向下弯曲约45 °，枕骨突起和寰椎棘之间出现菱形外观的可压低表面可见。将23 G针穿刺入小脑延髓池进行CSF收集，在该区域不做任何切口。将针的钝端插入10 in.将一段PE-50管和管的另一端连接到收集注射器。通过简单抽吸将未污染的样品吸入注射器中。这种技术很简单，可以由一个人完成。该技术具有大于95%的CSF收集成功率，并且没有红细胞污染。此外，每只大鼠产生100-120 μ L CSF。该方法简单，有效，易于执行，并已成功地应用于临床前筛选新的化学实体在中枢神经系统使用的神经药物治疗。通过研究卡马西平和雷氯必利的CSF浓度证明了本方法。(C)2008 Elsevier B. V.保留所有权利。
Many central nervous system (CNS) drug discovery programs require the successful collection of cerebrospinal fluid (CSF) for assessing CNS penetration and distribution of new chemical entities. The objective of the present investigation was to simplify the technique for collecting maximum CSF from cisterna magna of the rats. Rat was anesthetized with 5% halothane and positioned in a stereotaxic frame. The rat head was flexed downward at approximately 45, a depressible surface with the appearance of a rhomb between occipital protuberances and the spine of the atlas becomes visible. The 23 G needle was punctured info the cisterna magna for CSF collection without making any incision at this region. The blunt end of the needle was inserted into a 10 in. length of PE-50 tubing and other end of the tubing was connected to a collection syringe. The non-contaminated sample was drawn into the syringe by simple aspiration. This technique is simple and can be performed by one person. The technique has a greater than 95% success rate of CSF collection and it was free of red blood cell contamination. In addition, it yielded 100-120 mu L of CSF per rat. This method is simple, effective, and easy to perform and has been successfully applied in preclinical screening of novel chemical entities in neuropharmacotherapy for CNS use. The present method is demonstrated by studying the CSF concentrations of carbamazepine and raclopride. (C) 2008 Elsevier B.V. All rights reserved.