Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme

• Published in: Acta neuropathologica Vol. 105; no. 6; pp. 586 - 592
• Main Authors: WOLBURG, Hartwig, WOLBURG-BUCHHOLZ, Karen, KRAUS, Jörg, RASCHER-EGGSTEIN, Gesa, LIEBNER, Stefan, HAMM, Stefan, DUFFNER, Frank, GROTE, Ernst-H, RISAU, Werner, ENGELHARDT, Britta
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.06.2003; Springer Nature B.V
• Subjects: Animals; Autoimmune diseases; Biological and medical sciences; Blood Vessels - metabolism; Blood Vessels - pathology; Blood-Brain Barrier; Central Nervous System - metabolism; Central Nervous System - pathology; Claudin-3; Claudin-5; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Immunohistochemistry - methods; Medical sciences; Membrane Proteins - metabolism; Mice; Mice, Inbred Strains; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Occludin; Phosphoproteins - metabolism; Rodents; Tight Junctions - metabolism; Tight Junctions - pathology; Tumors of the nervous system. Phacomatoses; Zonula Occludens-1 Protein; Autoimmunity; Human; Immunohistochemistry; Edema formation; Nervous system diseases; Encephalomyelitis; Pathogenesis; Rodentia; Malignant tumor; Blood brain barrier; Glioblastoma multiforme; Cerebral disorder; Occludin; Pathology; Malignant glioma; Vertebrata; Claudins; Mammalia; Mouse; Blood-brain barrier; Animal; Central nervous system disease; Tight junction; Spinal cord disease
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-003-0688-z

In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB). During inflammation, BBB properties are frequently lost, resulting in brain edema. To investigate whether BBB leakiness correlates with molecular changes at BBB TJs, we performed immunofluorescence stainings for TJ molecules in a mouse model of experimental autoimmune encephalomyelitis (EAE) and in human tissue with glioblastoma multiforme (GBM). In TJs of healthy CNS vessels in both mouse and man we detected occludin, ZO-1, claudin-5 and claudin-3. In EAE brain and spinal cord sections we observed the selective loss of claudin-3 immunostaining from TJs of venules surrounded by inflammatory cuffs, whereas the localization of the other TJ proteins remained unchanged. In addition, selective loss of claudin-3 immunostaining was also observed in altered cerebral microvessels of human GBM. Our data demonstrate the selective loss of claudin-3 from BBB TJs under pathological conditions such as EAE or GBM when the integrity of the BBB is compromised, and therefore suggest that claudin-3 is a central component determining the integrity of BBB TJs in vivo.