In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space
RG Thorne, C Nicholson - Proceedings of the National Academy of …, 2006 - pnas.org
RG Thorne, C Nicholson
Proceedings of the National Academy of Sciences, 2006•pnas.orgDiffusion within the extracellular space (ECS) of the brain is necessary for chemical
signaling and for neurons and glia to access nutrients and therapeutics; however, the width
of the ECS in living tissue remains unknown. We used integrative optical imaging to show
that dextrans and water-soluble quantum dots with Stokes–Einstein diameters as large as
35 nm diffuse within the ECS of adult rat neocortex in vivo. Modeling the ECS as fluid-filled
“pores” predicts a normal width of 38–64 nm, at least 2-fold greater than estimates from EM …
signaling and for neurons and glia to access nutrients and therapeutics; however, the width
of the ECS in living tissue remains unknown. We used integrative optical imaging to show
that dextrans and water-soluble quantum dots with Stokes–Einstein diameters as large as
35 nm diffuse within the ECS of adult rat neocortex in vivo. Modeling the ECS as fluid-filled
“pores” predicts a normal width of 38–64 nm, at least 2-fold greater than estimates from EM …
Diffusion within the extracellular space (ECS) of the brain is necessary for chemical signaling and for neurons and glia to access nutrients and therapeutics; however, the width of the ECS in living tissue remains unknown. We used integrative optical imaging to show that dextrans and water-soluble quantum dots with Stokes–Einstein diameters as large as 35 nm diffuse within the ECS of adult rat neocortex in vivo. Modeling the ECS as fluid-filled “pores” predicts a normal width of 38–64 nm, at least 2-fold greater than estimates from EM of fixed tissue. ECS width falls below 10 nm after terminal ischemia, a likely explanation for the small ECS visualized in electron micrographs. Our results will improve modeling of neurotransmitter spread after spillover and ectopic release and establish size limits for diffusion of drug delivery vectors such as viruses, liposomes, and nanoparticles in brain ECS.
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