The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain
Abstract
Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes (BMs) of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial BMs of arteries. This project tested the hypotheses that pial-glial BM of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a 4.2-year-old dog, whereas the post-mortem electron microscopy was performed in a 12-year-old dog. We demonstrated a significant increase in the thickness of the pial-glial BM in the midbrain compared with the same BM in different regions of the brain and an increase in the convective influx of fluid from the subarachnoid space. These results are highly significant for the intrathecal drug delivery into the brain, indicating that the midbrain is better equipped for convective influx/glymphatic entry of the CSF.
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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 [10]
Cites
Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology
Abbott, N. J. (2004) · Neurochemistry International · doi:10.1016/j.neuint.2003.11.006 · Cited by 786 · see citing works
Vascular basement membranes as pathways for the passage of fluid into and out of the brain
Morris, A. W. J., Sharp, M. M., Albargothy, N. J., Fernandes, R., Hawkes, C. A., Verma, A., Weller, R. O., & Carare, R. O. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1555-z · Cited by 289 · see citing works
Self-citationEide, P. K., & Ringstad, G. (2015) · Acta Radiologica Open · doi:10.1177/2058460115609635 · Cited by 218 · see citing works
Carare, R. O., Hawkes, C. A., Jeffrey, M., Kalaria, R. N., & Weller, R. O. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12042 · Cited by 207 · see citing works
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Brain-wide glymphatic enhancement and clearance in humans assessed with MRI.
Ringstad, G., Valnes, L. M., Dale, A. M., Pripp, A. H., Vatnehol, S.-A. S., Emblem, K. E., Mardal, K.-A., & Eide, P. K. (2018) · JCI Insight · doi:10.1172/jci.insight.121537 · Cited by 533 · see citing works
“001 Thalamus [10, 49] 5 ± 21 2 ± 16 10 ± 22 10 ± 17 33 ± 27 20 ± 24 3 ± 17 <0.”
Albargothy, N. J., Johnston, D. A., MacGregor-Sharp, M., Weller, R. O., Verma, A., Hawkes, C. A., & Carare, R. O. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1862-7 · Cited by 311 · see citing works
Self-citationRapid lymphatic efflux limits cerebrospinal fluid flow to the brain
Ma, Q., Ries, M., Decker, Y., Müller, A., Riner, C., Bücker, A., Fassbender, K., Detmar, M., & Proulx, S. T. (2019) · Acta Neuropathologica · doi:10.1007/s00401-018-1916-x · Cited by 210 · see citing works
- Authors
- Dobson, H., Sharp, M. M., Cumpsty, R., Criswell, T. P., Wellman, T., Finucane, C., Sullivan, J. M., Weller, R. O., Verma, A., & Carare, R. O.
- Affiliations
- Western University (CA)
- Southampton General Hospital (GB)
- Invicro (United States) (US)
- Biogen (United States) (US)
- ORCID
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2017-11-13
- Volume
- 131
- Issue
- 22
- Pages
- 2745-2752
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W2763721270
- Cited by
- 27
- References
- 4
- Citations by year
- 2025: 1 · 2024: 8 · 2023: 1 · 2022: 2 · 2021: 4 · 2019: 6 · 2018: 5
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- University of Southampton
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- cerebrospinal fluid, glymphatic system, midbrain, basement membrane thickness, cerebral arteries, subarachnoid space, intrathecal drug delivery
- MeSH terms
- Animals, Arteries, Basement Membrane, Cerebrospinal Fluid, Dogs, Endothelium, Magnetic Resonance Imaging, Mesencephalon, Muscle, Smooth, Neuroglia, Pia Mater, Time Factors, Positron-Emission Tomography
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