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

点击翻译按钮获取中文摘要

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.