Assessment of blood-brain barrier function using near infrared fluorescence imaging techniques

使用近红外荧光成像技术评估血脑屏障功能

• 批准号: 371699-2009
• 负责人: Miller, Donald
• 金额: $ 1.82万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528337
• 关键词: Assessment; blood; brain; barrier; function

The brain capillary endothelial cells that form the blood-brain barrier have an important role in providing the proper environment for maintaining normal brain function. Under normal conditions, the blood-brain barrier restricts the movement of solutes, macromolecules and cells from the blood to the brain. While once considered to be a static cellular barrier, it is now understood that the permeability of the brain capillary endothelial cells forming the blood-brain barrier can be altered in response to physiological and pathophysiological factors as well as drug therapy. The ability to quantitatively monitor changes in blood-brain barrier function is crucial in understanding both disease progression as well as advancing treatment strategies for a number of neurological conditions. The objective of the current proposal is to use a series of near infrared fluorescent (NIRF) dyes to assess selected blood-brain barrier function at both the cellular and whole animal level. The advantage of the NIRF dye approach is the low background fluorescence and deep penetration of the fluorescence signal in the NIR wavelengths. The proposal will focus on several specific transport/permeability pathways, including transcellular solute and macromolecule transport into and out of the brain, as well as cell junction integrity and immune cell migration and traficking in the blood-brain barrier. The long term objective of this research is the development of a NIRF imaging platform that can be used to monitor important blood-brain barrier function and quantitatively assess the impact of physiological and pathophysiological events that lead to alterations in normal blood-brain barrier function and ultimately alterations in neurological activity.

形成血脑屏障的脑毛细血管内皮细胞在为维持正常脑功能提供适当环境方面具有重要作用。 在正常情况下，血脑屏障限制溶质、大分子和细胞从血液到大脑的运动。 虽然曾经被认为是静态的细胞屏障，但现在人们了解到，形成血脑屏障的脑毛细血管内皮细胞的渗透性可以根据生理和病理生理因素以及药物治疗而改变。 定量监测血脑屏障功能变化的能力对于了解疾病进展以及推进许多神经系统疾病的治疗策略至关重要。 目前的建议的目的是使用一系列的近红外荧光（NIRF）染料，以评估选定的血脑屏障功能，在细胞和整个动物的水平。 NIRF染料方法的优点是低背景荧光和NIR波长中荧光信号的深度穿透。 该提案将集中在几个特定的运输/渗透性途径，包括跨细胞溶质和大分子运输进出大脑，以及细胞连接的完整性和免疫细胞的迁移和traficking在血脑屏障。本研究的长期目标是开发一种NIRF成像平台，可用于监测重要的血脑屏障功能，并定量评估导致正常血脑屏障功能改变并最终改变神经活动的生理和病理生理事件的影响。