دورية أكاديمية
Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro-inflammation.
| العنوان: | Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro-inflammation. |
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| المؤلفون: | Kooij G; Department of Molecular Cell Biology and Immunology, Neuroscience Campus Amsterdam, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands, g.kooij@vumc.nl., Kopplin K, Blasig R, Stuiver M, Koning N, Goverse G, van der Pol SM, van Het Hof B, Gollasch M, Drexhage JA, Reijerkerk A, Meij IC, Mebius R, Willnow TE, Müller D, Blasig IE, de Vries HE |
| المصدر: | Acta neuropathologica [Acta Neuropathol] 2014 Aug; Vol. 128 (2), pp. 267-77. Date of Electronic Publication: 2013 Dec 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0412041 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0533 (Electronic) Linking ISSN: 00016322 NLM ISO Abbreviation: Acta Neuropathol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin : Springer Verlag |
| مواضيع طبية MeSH: | Choroid Plexus/*physiopathology , Claudin-3/*metabolism , Encephalomyelitis, Autoimmune, Experimental/*physiopathology , Multiple Sclerosis/*physiopathology, Adult ; Aged ; Aged, 80 and over ; Animals ; Brain/blood supply ; Brain/pathology ; Brain/physiopathology ; Choroid Plexus/pathology ; Claudin-3/genetics ; Disease Progression ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Humans ; Male ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Microvessels/pathology ; Microvessels/physiopathology ; Middle Aged ; Multiple Sclerosis/pathology ; Myelin-Oligodendrocyte Glycoprotein ; Peptide Fragments ; Severity of Illness Index |
| مستخلص: | 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. |
| المشرفين على المادة: | 0 (CLDN3 protein, human) 0 (Claudin-3) 0 (Cldn3 protein, mouse) 0 (Myelin-Oligodendrocyte Glycoprotein) 0 (Peptide Fragments) 0 (myelin oligodendrocyte glycoprotein (35-55)) |
| تواريخ الأحداث: | Date Created: 20131221 Date Completed: 20150226 Latest Revision: 20140718 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1007/s00401-013-1227-1 |
| PMID: | 24356983 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1432-0533 |
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| DOI: | 10.1007/s00401-013-1227-1 |