title: Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain.
abstract: In the brain, a paravascular space exists between vascular cells and astroglial end-foot processes, creating a continuous sheath surrounding blood vessels. Using in vivo two-photon imaging we demonstrate that the paravascular circulation facilitates selective transport of small lipophilic molecules, rapid interstitial fluid movement and widespread glial calcium signaling. Depressurizing the paravascular system leads to unselective lipid diffusion, intracellular lipid accumulation and pathological signaling in astrocytes. As the central nervous system is devoid of lymphatic vessels, the paravascular space may serve as a lymphatic equivalent that represents a separate highway for the transport of lipids and signaling molecules.
authors.affiliation: 1] Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642 [2] Letten Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway [3] Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway [4].
authors.forename: Vinita
authors.initials: V
authors.lastname: Rangroo Thrane
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Thrane
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Plog
authors.forename: Meenakshisundaram
authors.initials: M
authors.lastname: Thiyagarajan
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Iliff
authors.forename: Rashid
authors.initials: R
authors.lastname: Deane
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation; D018613:Microscopy, Confocal; D057054:Molecular Imaging / Q000379:methods; D015398:Signal Transduction
chemical_list: D005456:Fluorescent Dyes; D002118:Calcium