MRI of whole rat brain perivascular network reveals role for ventricles in brain waste clearance
Open accessAbstract
Investigating the mechanisms by which metabolic wastes are cleared from nervous tissue is important for understanding natural function and the pathophysiology of several neurological disorders including Alzheimer’s disease. Recent evidence suggests clearance may be the function of annular spaces around cerebral blood vessels, called perivascular spaces (PVS), through which cerebrospinal fluid (CSF) is transported from the subarachnoid space into brain parenchyma to exchange with interstitial fluid (also known as the glymphatic system). In this work, an MRI-based methodology was developed to reconstruct the PVS network in whole rat brain to better elucidate both PVS uptake and clearance pathways. MR visible tracer (Gd-albumin) was infused in vivo into the CSF-filled lateral ventricle followed by ex vivo high-resolution MR imaging at 17.6 T with an image voxel volume two orders of magnitude smaller than previously reported. Imaged tracer distribution patterns were reconstructed to obtain a more complete brain PVS network. Several PVS connections were repeatedly highlighted across different animals, and new PVS connections between ventricles and different parts of the brain parenchyma were revealed suggesting a possible role for the ventricles as a source or sink for solutes in the brain. In the future, this methodology may be applied to understand changes in the PVS network with disease.
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Prior studies have shown that albumin-binding dyes have reduced clearance to the periphery after ICV infusion in mice and accumulate in perivascular compartments after ICV injection in rats.
“because prior studies have shown that albumin-binding dyes have reduced clearance to the periphery after ICV infusion in mice [23] and accumulate in perivascular compartments after ICV injection in rats [24, 25].”
From Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid (2025) · cites this paper as [25]
Albumin-binding dyes have reduced clearance to the periphery after ICV infusion in mice and accumulate in perivascular compartments after ICV injection in rats.
“Prior studies have shown that albumin-binding dyes have reduced clearance to the periphery after intracerebroventricular (ICV) infusion in mice28 and accumulate in perivascular compartments after ICV injection in rats.15,29”
From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [29]
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Sorted by citations
Sorets, A. G., Schwensen, K. R., Francini, N., Kjar, A., Abdulrahman, A. M., Shostak, A., Katdare, K. A., Schoch, K. M., Cowell, R. P., Park, J. C., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf600 · Cited by 6 · see citing works
Sorets, A., Schwensen, K., Francini, N., Kjar, A., Abdulrahman, A., Shostak, A., Katdare, K., Schoch, K., Cowell, R., Park, J., et al. (2024) · doi:10.1101/2024.06.09.598079 · Cited by 4 · see citing works
“15,29 We recently developed a lipid-siRNA conjugate termed “L2-siRNA” that was optimized in the context of intravenous delivery for albumin hitchhiking toward delivery to tumors.”
- Authors
- Magdoom, K. N., Brown, A., Rey, J., Mareci, T. H., King, M. A., & Sarntinoranont, M.
- Affiliations
- University of Florida (US)
- Veterans Health Administration (US)
- Corresponding author
- Sarntinoranont, Malisa
- Venue
- Scientific Reports
- Published
- 2019-08-07
- Volume
- 9
- Issue
- 1
- Pages
- 11480-11480
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6685961
- OpenAlex
- W2965530449
- Cited by
- 35
- References
- 9
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 2
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (DMR-1157490)
- U.S. Department of Health & Human Services | National Institutes of Health (1S10OD020026)
- Chiari and Syringomyelia Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- perivascular spaces, glymphatic system, cerebrospinal fluid, brain waste clearance, lateral ventricle, rat brain, Alzheimer's disease, interstitial fluid
- MeSH terms
- Glymphatic System, Albumins, Alzheimer Disease, Animals, Cerebral Ventricles, Cerebrospinal Fluid, Contrast Media, Evans Blue, Feasibility Studies, Magnetic Resonance Imaging, Male, Subarachnoid Space, Gadolinium DTPA, Models, Animal, Rats, Infusions, Intraventricular
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