Affiliations: UCSF MS Center, San Francisco, CA, USA
Note: [] Corresponding author: UCSF Multiple Sclerosis Center, 350
Parnassus Avenue, suite 908, San Francisco, CA 94117, USA. Tel.: +1 415 514
2468; Fax: +1 415 514 2443; E-mail: waubant@itsa.ucsf.edu
Abstract: Blood-brain barrier (BBB) disruption is one of the hallmarks of
multiple sclerosis (MS). It is incompletely understood whether BBB disruption
is the initial MS event leading to MS lesion formation or whether it is merely
a consequence of cellular infiltration in the central nervous system (CNS). The
presence of gadolinium enhancing (Gd+) lesions on serial brain MRI scans
is frequently used to evaluate BBB disruption. The presence of Gd enhancement
has therefore been used as a reference for most works evaluating promising
biomarkers of BBB disruption that are reviewed here. These promising biomarkers
include cytokines and chemokines, and their receptors, cell surface markers,
and matrix metalloproteinases and their natural inhibitors. At this time, none
of these markers have been shown as sensitive as the presence of Gd enhancement
to reflect BBB disruption. However, MRI scanning is not only unpractical and
expensive; it may also under represent the overall extent of BBB disruption.
Developing new MS biomarkers that are sensitive and specific for BBB disruption
could 1) improve the monitoring of disease activity; 2) improve the monitoring
of response to MS therapies which target BBB disruption; and 3) advance our
understanding of dynamic MS processes participating in BBB disruption.
