Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways.
Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid.
1 Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
Beatrice
B
Bedussi
2 Department of Cell Biology and Histology, Electron Microscopy Centre Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Nicole N
NN
van der Wel
1 Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
Judith
J
de Vos
2 Department of Cell Biology and Histology, Electron Microscopy Centre Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Henk
H
van Veen
1 Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
Maria
M
Siebes
1 Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
Ed
E
VanBavel
1 Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
Erik Ntp
EN
Bakker
D000818:Animals; D001808:Blood Vessels / Q000000981:diagnostic imaging* / Q000648:ultrastructure; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000648:ultrastructure; D002552:Cerebral Ventricles / Q000098:blood supply / Q000000981:diagnostic imaging / Q000648:ultrastructure; D002555:Cerebrospinal Fluid / Q000000981:diagnostic imaging*; D002946:Cisterna Magna / Q000000981:diagnostic imaging / Q000648:ultrastructure; D003911:Dextrans; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000648:ultrastructure; D045604:Extracellular Fluid / Q000000981:diagnostic imaging; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D011921:Rats, Inbred WKY; D013346:Subarachnoid Space
D003911:Dextrans
Cerebrospinal fluid; glymphatic pathway; interstitial fluid; paravascular space; subarachnoid space