IN VITRO MODEL OF THE BLOOD-BRAIN BARRIER

在未来几年，神经系统疾病的治疗将是 这在很大程度上取决于新治疗剂的开发， 对已经存在的化合物进行改造。 血脑 屏障将大多数药物挡在大脑之外，并严重限制了药物的释放。 有用性 因此，制药公司将需要筛选许多 化合物进入大脑，也将不得不考虑 各种旨在克服血脑屏障的策略。 目前，通过将化合物注射到大量的 动物，要么观察间接和繁琐，也提高 重要的动物福利问题。 血脑细胞培养模型的建立 屏障既有利于快速筛选能够进入的化合物， 大脑，也将允许系统地使用细胞和分子 生物进入大脑，也将允许系统地使用 细胞和分子生物学技术来开发药物输送系统。 在这个建议中，我们描述了一种技术， 细胞，使它们形成，细胞培养物，相当于血液- 脑屏障 我们详细介绍了一组实验，将使这个模型 神经系统感兴趣的团体常规使用的系统 治疗学 我们还描述了这种模型系统可以被 用于探索药物输送到大脑的新模式。

In the coming years, the treatment of neurological disorders will be largely dependent on the development of new therapeutic agents and the modification of those compounds already in existence. The blood-brain barrier keeps most drugs out of the brain and severely limits their usefulness. Pharmaceutical companies will, therefore, need to screen many compounds for their entry into the brain and will also have to consider a variety of strategies designed to overcome the blood-brain barrier. Currently, compounds are screened by injecting them into large numbers of animals and either observing indirect and cumbersome and also raise important animal welfare concerns. A cell culture model of the blood-brain barrier would both facilitate rapid screening for compounds able to enter the brain and would also allow the systematic use of cell and molecular biological to enter the brain and would also allow the systematic use of cell and molecular biological techniques to develop drug delivery systems. In this proposal, we describe a technique for growing brain endothelial cells such that they form, the cell culture, an equivalent of the blood- brain barrier. We detail a set of experiments that will enable this model system to be used routinely by groups interested in nervous system therapeutics. We also describe ways in which this model system can be utilized to explore novel modes of drug delivery to the brain.