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Vascular basement membranes as pathways for the passage of fluid into and out of the brain

Vascular basement membranes as pathways for the passage of fluid into and out of the brain
Vascular basement membranes as pathways for the passage of fluid into and out of the brain

In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

Actins, Amyloid beta-Peptides, Animals, Basement Membrane, Biotinylation, Blood Vessels, Cerebrospinal Fluid, Cisterna Magna, Extracellular Space, Fluorescent Dyes, Hippocampus, Laminin, Male, Metal Nanoparticles, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Peptide Fragments, Journal Article, Research Support, Non-U.S. Gov't
0001-6322
725-736
Morris, Alan W.J.
e70d7160-c9d9-4035-90b8-9006a1052551
Sharp, Matthew MacGregor
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Albargothy, Nazira J.
ec692e7e-550c-4914-a7c6-c8eb934b1a0f
Fernandes, Rute
848317d8-1eb0-48ad-aefc-012ab19d9f52
Hawkes, Cheryl A
031a17ac-0931-4ff9-93cc-df8cb58e14f7
Verma, Ajay
5a207350-0de9-487a-be28-f9eb2f558140
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Morris, Alan W.J.
e70d7160-c9d9-4035-90b8-9006a1052551
Sharp, Matthew MacGregor
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Albargothy, Nazira J.
ec692e7e-550c-4914-a7c6-c8eb934b1a0f
Fernandes, Rute
848317d8-1eb0-48ad-aefc-012ab19d9f52
Hawkes, Cheryl A
031a17ac-0931-4ff9-93cc-df8cb58e14f7
Verma, Ajay
5a207350-0de9-487a-be28-f9eb2f558140
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa

Morris, Alan W.J., Sharp, Matthew MacGregor, Albargothy, Nazira J., Fernandes, Rute, Hawkes, Cheryl A, Verma, Ajay, Weller, Roy O and Carare, Roxana O. (2016) Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Acta Neuropathologica, 131 (5), 725-736. (doi:10.1007/s00401-016-1555-z).

Record type: Article

Abstract

In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

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10.1007%2Fs00401-016-1555-z - Version of Record
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Accepted/In Press date: 26 February 2016
e-pub ahead of print date: 14 March 2016
Published date: May 2016
Keywords: Actins, Amyloid beta-Peptides, Animals, Basement Membrane, Biotinylation, Blood Vessels, Cerebrospinal Fluid, Cisterna Magna, Extracellular Space, Fluorescent Dyes, Hippocampus, Laminin, Male, Metal Nanoparticles, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Peptide Fragments, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 420455
URI: https://eprints.soton.ac.uk/id/eprint/420455
ISSN: 0001-6322
PURE UUID: ee20ca4a-56a0-40a0-8c5f-9f165e29ba53
ORCID for Matthew MacGregor Sharp: ORCID iD orcid.org/0000-0002-6623-5078
ORCID for Nazira J. Albargothy: ORCID iD orcid.org/0000-0003-1435-8612

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Date deposited: 08 May 2018 16:30
Last modified: 03 Dec 2019 01:41

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Contributors

Author: Alan W.J. Morris
Author: Matthew MacGregor Sharp ORCID iD
Author: Nazira J. Albargothy ORCID iD
Author: Rute Fernandes
Author: Cheryl A Hawkes
Author: Ajay Verma
Author: Roy O Weller

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