The University of Southampton
University of Southampton Institutional Repository

Pathophysiology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis

Pathophysiology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis
Pathophysiology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis
In most organs of the body, immunological reactions involve the drainage of antigens and antigen presenting cells (APCs) along defined lymphatic channels to regional lymph nodes. The CNS is considered to be an immunologically privileged organ with no conventional lymphatics. However, immunological reactions do occur in the CNS in response to infections and in immune-mediated disorders such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Here, we review evidence that cervical lymph nodes play a role in B and T cell mediated immune reactions in the CNS. Then we define the separate pathways by which interstitial fluid (ISF) and CSF drain to cervical lymph nodes. ISF and solutes drain from the brain along the 100-150nm-wide basement membranes in the walls of capillaries and arteries. In humans, this perivascular pathway is outlined by the deposition of insoluble amyloid (Abeta) in capillary and artery walls in cerebral amyloid angiopathy in Alzheimer's disease. The failure of APCs to migrate to lymph nodes along perivascular lymphatic drainage pathways may be a major factor in immunological privilege of the brain. Lymphatic drainage of CSF is predominantly through the cribriform plate into nasal lymphatics. Lymphatic drainage of ISF and CSF and the specialised cervical lymph nodes to which they drain play significant roles in the induction of immunological tolerance and of adaptive immunological responses in the CNS. Understanding the afferent and efferent arms of the CNS lymphatic system will be valuable for the development of therapeutic strategies for diseases such as MS
multiple sclerosis, lymphatic drainage of the central nervous system, interstitial fluid, cerebrospinal fluid, cerebral amyloid angiopathy, t cells, lymphocyte trafficking, imprinting, dendritic cells, tolerance
0928-4680
295-306
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Carare, Roxanna O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Minagar, Alireza
909fee49-531c-4104-820b-9a478cb07dac
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Carare, Roxanna O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Minagar, Alireza
909fee49-531c-4104-820b-9a478cb07dac

Weller, Roy O., Galea, Ian, Carare, Roxanna O. and Minagar, Alireza (2010) Pathophysiology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis. Pathophysiology, 17 (4), 295-306. (doi:10.1016/j.pathophys.2009.10.007).

Record type: Article

Abstract

In most organs of the body, immunological reactions involve the drainage of antigens and antigen presenting cells (APCs) along defined lymphatic channels to regional lymph nodes. The CNS is considered to be an immunologically privileged organ with no conventional lymphatics. However, immunological reactions do occur in the CNS in response to infections and in immune-mediated disorders such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Here, we review evidence that cervical lymph nodes play a role in B and T cell mediated immune reactions in the CNS. Then we define the separate pathways by which interstitial fluid (ISF) and CSF drain to cervical lymph nodes. ISF and solutes drain from the brain along the 100-150nm-wide basement membranes in the walls of capillaries and arteries. In humans, this perivascular pathway is outlined by the deposition of insoluble amyloid (Abeta) in capillary and artery walls in cerebral amyloid angiopathy in Alzheimer's disease. The failure of APCs to migrate to lymph nodes along perivascular lymphatic drainage pathways may be a major factor in immunological privilege of the brain. Lymphatic drainage of CSF is predominantly through the cribriform plate into nasal lymphatics. Lymphatic drainage of ISF and CSF and the specialised cervical lymph nodes to which they drain play significant roles in the induction of immunological tolerance and of adaptive immunological responses in the CNS. Understanding the afferent and efferent arms of the CNS lymphatic system will be valuable for the development of therapeutic strategies for diseases such as MS

Text
__soton.ac.uk_ude_personalfiles_users_ig1_mydesktop_Staff profile_Galea et al 2010_Pathophysiology.pdf - Version of Record
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 23 October 2009
e-pub ahead of print date: December 2009
Published date: 1 September 2010
Keywords: multiple sclerosis, lymphatic drainage of the central nervous system, interstitial fluid, cerebrospinal fluid, cerebral amyloid angiopathy, t cells, lymphocyte trafficking, imprinting, dendritic cells, tolerance

Identifiers

Local EPrints ID: 73554
URI: http://eprints.soton.ac.uk/id/eprint/73554
ISSN: 0928-4680
PURE UUID: ee66c5d6-9da8-4bcb-ab53-abbafdbaff5f
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

Catalogue record

Date deposited: 10 Mar 2010
Last modified: 10 Dec 2019 01:46

Export record

Altmetrics

Contributors

Author: Roy O. Weller
Author: Ian Galea ORCID iD
Author: Alireza Minagar

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×