Evidence for a ‘Paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space
Abstract
The protein tracer, horseradish peroxidase (HRP), was infused into the lateral cerebral ventricles or subarachnoid space of anesthetized cats and dogs after insertion of a cisternal cannula to permit drainage of cerebrospinal fluid (CSF) and tracer solution. The intracerebral distribution of the tracer was then determined by light microscopy of serial brain sections after postinfusion intervals of 4 min-2 h. For the localization of HRP, sections were incubated with diaminobenzidine (DAB) or the much more sensitive chromogen, tetramethylbenzidine (TMB). The TMB reaction showed a consistent 'paravascular' distribution of tracer reaction product, within the perivascular spaces (PVS) around large penetrating vessels and in the basal laminae around capillaries, far beyond the termination of the PVS. After infusion of HRP over 4 min, arterioles were surrounded by the tracer, but capillaries and venules were usually less densely demarcated; by 6 min, however, the intraparenchymal microvasculature was outlined in toto throughout the forebrain and brainstem. Electron microscopy of sections incubated in DAB after 10 or 20 min HRP circulation confirmed the paravascular location of the reaction product, which was also dispersed throughout the extracellular spaces (ECS) of the adjacent parenchyma. Our results demonstrate that solutes in the CSF have access to the ECS throughout the neuraxis within minutes via fluid pathways paralleling the intraparenchymal vasculature. The rapid paravascu…
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Animal studies have shown communication between the subarachnoid CSF space and perivascular compartments of the brain and spinal cord.
“Previous animal studies have shown communication between the subarachnoid cerebrospinal fluid (CSF) space and perivascular compartments of the brain (6-10) and spinal cord (11).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [6]
Early studies have suggested that solutes injected into the subarachnoid space can use paravascular transport from the subarachnoid space to enter the brain through Virchow-Robin spaces in the same direction as the flow of blood.
“Early studies have suggested that solutes injected into the subarachnoid space can use paravascular transport from the subarachnoid space to enter the brain through VirchowRobin spaces in the same direction to the flow of blood (496).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [496]
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- Authors
- Rennels, M. L., Gregory, T. F., Blaumanis, O. R., Fujimoto, K., & Grady, P. A.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Rennels, Marshall L.
- ORCID
- Fujimoto, Katsukuni
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1985-02
- Volume
- 326
- Issue
- 1
- Pages
- 47-63
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2021493191
- Cited by
- 752
- References
- 2
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 35 · 2023: 33 · 2022: 50 · 2021: 50 · 2020: 34 · 2019: 38 · 2018: 42 · 2017: 32 · 2016: 25 · 2015: 18 · 2014: 27 · 2013: 20 · 2012: 15
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50ns016332-08)
- National Institute of Neurological Disorders and Stroke (3 P50 NS 16332)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- cerebrospinal fluid, perivascular spaces, horseradish peroxidase tracer, subarachnoid space, cerebral microvasculature, extracellular space, dogs
- MeSH terms
- Anesthesia, General, Animals, Arteries, Arterioles, Biological Transport, Brain, Cats, Cerebrospinal Fluid, Female, Male, Nerve Tissue Proteins, Pulse, Subarachnoid Space
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