In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space.

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  • Author(s): Thorne RG;Thorne RG; Nicholson C
  • Source:
    Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2006 Apr 04; Vol. 103 (14), pp. 5567-72. Date of Electronic Publication: 2006 Mar 27.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Quantum Theory*; Dextrans/*metabolism ; Extracellular Space/*metabolism ; Neocortex/*metabolism; Animals ; Diffusion ; Female ; Nanotechnology ; Rats ; Rats, Sprague-Dawley
    • Abstract:
      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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    • Grant Information:
      R01 NS028642 United States NS NINDS NIH HHS; R01 NS 28642 United States NS NINDS NIH HHS
    • Accession Number:
      0 (Dextrans)
    • Publication Date:
      Date Created: 20060329 Date Completed: 20060606 Latest Revision: 20220309
    • Publication Date:
      20240829
    • Accession Number:
      PMC1459394
    • Accession Number:
      10.1073/pnas.0509425103
    • Accession Number:
      16567637