title: Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system.
abstract: BACKGROUND
  In the absence of a true lymphatic system in the brain parenchyma, alternative clearance pathways for excess fluid and waste products have been proposed. Suggested mechanisms for clearance implicate a role for brain interstitial and cerebrospinal fluids. However, the proposed direction of flow, the anatomical structures involved, and the driving forces are controversial.
  
  
  METHODS
  To trace the distribution of interstitial and cerebrospinal fluid in the brain, and to identify the anatomical structures involved, we infused a mix of fluorescent tracers with different sizes into the cisterna magna or striatum of mouse brains. We subsequently performed confocal fluorescence imaging of horizontal brain sections and made 3D reconstructions of the mouse brain and vasculature.
  
  
  RESULTS
  We observed a distribution pattern of tracers from the parenchyma to the ventricular system, from where tracers mixed with the cerebrospinal fluid, reached the subarachnoid space, and left the brain via the cribriform plate and the nose. Tracers also entered paravascular spaces around arteries both after injection in the cisterna magna and striatum, but this appeared to be of minor importance.
  
  
  CONCLUSIONS
  These data suggest a bulk flow of interstitial fluid from the striatum towards the adjacent lateral ventricle. Tracers may enter arterial paravascular spaces from two sides, both through bulk flow from the parenchyma and through mixing of CSF in the subarachnoid space. Disturbances in this transport pathway could influence the drainage of amyloid β and other waste products, which may be relevant for the pathophysiology of Alzheimer's disease.
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. b.bedussi@amc.uva.nl.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bedussi
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. m.g.vanlier@amc.uva.nl.
authors.forename: Monique G J T B
authors.initials: MG
authors.lastname: van Lier
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. jbartstra@hotmail.com.
authors.forename: Jonas W
authors.initials: JW
authors.lastname: Bartstra
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. j.devos@amc.uva.nl.
authors.forename: Judith
authors.initials: J
authors.lastname: de Vos
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. m.siebes@amc.uva.nl.
authors.forename: Maria
authors.initials: M
authors.lastname: Siebes
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. e.vanbavel@amc.uva.nl.
authors.forename: Ed
authors.initials: E
authors.lastname: VanBavel
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Room L0-119. Meibergdreef 9, PO Box: 22660, 1105 AZ, Amsterdam, The Netherlands. n.t.bakker@amc.uva.nl.
authors.forename: Erik N T P
authors.initials: EN
authors.lastname: Bakker
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002552:Cerebral Ventricles / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism; D002946:Cisterna Magna / Q000378:metabolism*; D004396:Coloring Agents / Q000378:metabolism; D018481:Convection; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004396:Coloring Agents