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Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases

Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases
Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases
The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance.
0272-4340
181-194
Bakker, Erik N.T.P.
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Bacskai, Brian J.
3d57b586-6b42-4e75-93c8-dfa86e8c21da
Arbel-Ornath, Michal
3bface26-c6bc-4350-9239-ee27e753c942
Aldea, Roxana
25e7ffd4-4adf-4591-942f-baed93a0b3ee
Bedussi, Beatrice
f4f58a0c-e036-4b69-a2a6-c88f46cf2504
Morris, Alan W.J.
e70d7160-c9d9-4035-90b8-9006a1052551
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Bakker, Erik N.T.P.
5011ae15-0aa7-46e1-9381-8fdd50b2b458
Bacskai, Brian J.
3d57b586-6b42-4e75-93c8-dfa86e8c21da
Arbel-Ornath, Michal
3bface26-c6bc-4350-9239-ee27e753c942
Aldea, Roxana
25e7ffd4-4adf-4591-942f-baed93a0b3ee
Bedussi, Beatrice
f4f58a0c-e036-4b69-a2a6-c88f46cf2504
Morris, Alan W.J.
e70d7160-c9d9-4035-90b8-9006a1052551
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa

Bakker, Erik N.T.P., Bacskai, Brian J., Arbel-Ornath, Michal, Aldea, Roxana, Bedussi, Beatrice, Morris, Alan W.J., Weller, Roy O. and Carare, Roxana O. (2016) Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases. Cellular and Molecular Neurobiology, 36 (2), 181-194. (doi:10.1007/s10571-015-0273-8). (PMID:26993512)

Record type: Article

Abstract

The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance.

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Accepted/In Press date: 18 September 2015
e-pub ahead of print date: 18 March 2016
Published date: March 2016
Organisations: Institute for Life Sciences

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Local EPrints ID: 397945
URI: https://eprints.soton.ac.uk/id/eprint/397945
ISSN: 0272-4340
PURE UUID: 8ef4c37f-6842-4cfa-be9c-bba713efc18b

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Date deposited: 12 Jul 2016 10:40
Last modified: 16 Jul 2019 19:47

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