Format

Send to

Choose Destination
Cell Mol Neurobiol. 2016 Mar;36(2):181-94. doi: 10.1007/s10571-015-0273-8. Epub 2016 Mar 18.

Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases.

Author information

1
Department of Biomedical Engineering and Physics, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
2
Massachusetts General Hospital, Charlestown, MA, 02129, USA.
3
Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK.
4
Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.
5
Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK. rcn@soton.ac.uk.
6
Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. rcn@soton.ac.uk.

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 (Aβ). 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 Aβ 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 Aβ 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 Aβ. 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.

KEYWORDS:

Cerebrospinal fluid; Cerebrovascular basement membranes; Interstitial fluid; Paravascular; Perivascular

PMID:
26993512
PMCID:
PMC4844641
DOI:
10.1007/s10571-015-0273-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center