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

14TSB_NAT Neurotox：一种新颖的集成 BBB 脑模型，用于综合药物渗透性和毒性测试

• 批准号: BB/M013111/1
• 负责人: Sikha Saha
• 金额: $ 10.5万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM013111%2F1
• 关键词: 14TSB_NAT; Neurotox; novel; integrated; BBB

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.

血脑屏障（BBB）由不同的专门细胞类型组成，并调节血液与大脑之间的物质交换。有大量疾病，包括中风，脑外伤和肿瘤，其中BBB的渗透性增加。相反，许多药物无法跨越BBB以使BBB成为治疗脑疾病的主要障碍之一。因此，对BBB的适当调节和维持对于有效输送大脑的药物以治愈脑部疾病并防止其进一步损害至关重要。在该项目中，我们旨在使用Kirkstall Quasi-Vivo系统开发三维体外BBB模型，该系统允许在相互连接的培养室中培养多种细胞类型，并通过一种方法，一种测定了通过通过BBB跨BBB的方法来培养的。电化学和激光生物传感器。该体外模型将是研究BBB功能不同方面的重要工具，并测试潜在药物的渗透性和毒性，并减少该领域的动物使用情况。基于人类细胞的模型应该比动物更准确和预测。

项目成果

A novel method to create an In vitro dynamic blood brain barrier model

一种创建体外动态血脑屏障模型的新方法

• 发表时间: 2016
• 作者: Miranda-Azpiazu P

A three dimensional (3D) human in vitro blood-brain barrier (BBB)

三维 (3D) 人体体外血脑屏障 (BBB)

• 发表时间: 2016
• 作者: Miranda-Azpiazu P

Selective cellular imaging with lanthanide-based upconversion nanoparticles.

• DOI: 10.1002/jbio.201800256
• 发表时间: 2019-04
• 期刊: Journal of biophotonics
• 影响因子: 2.8
• 作者: Nampi PP;Vakurov A;Mackenzie LE;Scrutton NS;Millner PA;Jose G;Saha S
• 通讯作者: Saha S

A novel in vitro 3D blood brain barrier for comprehensive drug permeability and toxicity testing

用于综合药物渗透性和毒性测试的新型体外 3D 血脑屏障

• 发表时间: 2015
• 作者: Miranda-Azpiazu P

A novel dynamic multicellular co-culture system for studying individual blood-brain barrier cell types in brain diseases and cytotoxicity testing.

• DOI: 10.1038/s41598-018-26480-8
• 发表时间: 2018-06-08
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Miranda-Azpiazu P;Panagiotou S;Jose G;Saha S
• 通讯作者: Saha S