14TSB_NAT Neurotox: A novel integrated BBB-brain model for comprehensive drug permeability and toxicity testing

血脑屏障(BBB)由不同的特殊细胞类型组成，调节血液和大脑之间的物质交换。在许多疾病中，包括中风、脑损伤和肿瘤，血脑屏障的通透性增加。相反，许多药物无法跨越血脑屏障到达大脑，使血脑屏障成为治疗脑部疾病的主要障碍之一。因此，适当地调节和维持血脑屏障对于有效地将药物输送到大脑以治疗脑部疾病和防止其进一步损害是至关重要的。在这个项目中，我们的目标是利用Kirkstall准活体系统建立一个三维的体外血脑屏障模型，该系统允许在相互连接的培养室内培养多种细胞类型，并建立一种通过电化学和激光生物传感器来测试潜在药物通过血脑屏障的方法。这一体外模型将为研究血脑屏障功能的不同方面、测试潜在药物的通透性和毒性以及减少动物在这一领域的使用提供重要工具。基于人类细胞的模型应该比动物更准确和更具预测性。

The blood-brain barrier (BBB) is composed of different specialised cell types and regulates exchange of substances between the blood and the brain. There are a large number of diseases including stroke, brain trauma and tumours in which the permeability of the BBB is increased. Conversely, many drugs are unable to cross the BBB to reach the brain making the BBB one of the major obstacles in the treatment of the brain diseases. Proper regulation and maintenance of BBB is, therefore, essential for effective drug delivery to the brain to cure brain diseases and preventing its further damage. In this project we aim to develop a three dimensional in vitro BBB model using the Kirkstall Quasi-Vivo system which allows multiple cell types to be cultured in inter-connected culture chambers and a method of assaying the passage of of potential drugs across the BBB by electrochemical and laser bio-sensors. This in vitro model will be an important tool for investigation of different aspects of BBB function and testing potential drugs for their permeability and toxicity and reducing animal usage in this area. Human cell based models should be more accurate and predictive than animals.