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Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro-inflammation

Official URL:https://doi.org/10.1007/s00401-013-1227-1
PubMed:View item in PubMed
Creators Name:Kooij, G. and Kopplin, K. and Blasig, R. and Stuiver, M. and Koning, N. and Goverse, G. and van der Pol, S.M.A. and van het Hof, B. and Gollasch, M. and Drexhage, J.A.R. and Reijerkerk, A. and Meij, I.C. and Mebius, R. and Willnow, T.E. and Mueller, D. and Blasig, I.E. and de Vries, H.E.
Journal Title:Acta Neuropathologica
Journal Abbreviation:Acta Neuropathol
Volume:128
Number:2
Page Range:267-277
Date:August 2014
Keywords:Multiple Sclerosis, Choroid Plexus, Claudin-3, Neuro-Inflammation, Blood-Cerebrospinal Fluid Barrier, Animals, Mice
Abstract:Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models recently implied that the passage of leukocytes across the brain vasculature is preceded by their traversal across the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus. The correlation between the presence of leukocytes in the CSF of patients suffering from MS and the number of inflammatory lesions as detected by magnetic resonance imaging suggests that inflammation at the choroid plexus contributes to the disease, although in a yet unknown fashion. We here provide first insights into the involvement of the choroid plexus in the onset and severity of the disease and in particular address the role of the tight junction protein claudin-3 (CLDN3) in this process. Detailed analysis of human post-mortem brain tissue revealed a selective loss of CLDN3 at the choroid plexus in MS patients compared to control tissues. Importantly, mice that lack CLDN3 have an impaired BCSFB and experience a more rapid onset and exacerbated clinical signs of experimental autoimmune encephalomyelitis, which coincides with enhanced levels of infiltrated leukocytes in their CSF. Together, this study highlights a profound role for the choroid plexus in the pathogenesis of multiple sclerosis, and implies that CLDN3 may be regarded as a crucial and novel determinant of BCSFB integrity.
ISSN:0001-6322
Publisher:Springer (Germany)
Item Type:Article

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