Blood-brain barrier alterations in the cerebral cortex in experimental autoimmune encephalomyelitis

Journal of Neuropathology and Experimental Neurology

Volumn 71, Issue 10, 2012, Pages 840-854

  Errede, Mariella ^a   Girolamo, Francesco ^b   Ferrara, Giovanni ^a   Strippoli, Maurizio ^a   Morando, Sara ^c   Boldrin, Valentina ^b   Rizzi, Marco ^a   Uccelli, Antonio ^c   Perris, Roberto ^d,e   Bendotti, Caterina ^b   Salmona, Mario ^b   Roncali, Luisa ^a   Virgintino, Daniela ^a  

^a UNIVERSITY OF BARI MEDICAL SCHOOL   (Italy)

^b MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^c UNIVERSITY OF GENOA   (Italy)

^d UNIVERSITY OF PARMA   (Italy)

^e CENTRO DI RIFERIMENTO ONCOLOGICO   (Italy)

Author keywords

Blood brain barrier; Cerebral cortex demyelination; Claudin 5; Experimental autoimmune encephalomyelitis; Inflammation; Occludin; Oligodendrocyte precursor cells

Indexed keywords

CAVEOLIN 1; CLAUDIN 5; FLUORESCEIN ISOTHIOCYANATE DEXTRAN; OCCLUDIN; PERTUSSIS TOXIN;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; BRAIN CORTEX; CELL ACTIVATION; CHRONIC DISEASE; CONTROLLED STUDY; DEMYELINATION; FEMALE; IMMUNOLOCALIZATION; INFLAMMATORY INFILTRATE; MICROGLIA; MICROVASCULAR ENDOTHELIAL CELL; MICROVASCULATURE; MOUSE; NEUROPIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; TIGHT JUNCTION;

ANIMALS; BLOOD-BRAIN BARRIER; CAVEOLIN 1; CEREBRAL CORTEX; CLAUDIN-5; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; GLUCOSE TRANSPORTER TYPE 1; MICE; MICE, INBRED C57BL; OCCLUDIN;

EID: 84866662273     PISSN: 00223069     EISSN: 15546578     Source Type: Journal    
DOI: 10.1097/NEN.0b013e31826ac110     Document Type: Article

References (135)

1. Allen IV, Kirk J. The anatomical and molecular pathology of multiple sclerosis. In: Russell WC, ed. Molecular Biology of Multiple Sclerosis. New York, NY: John Wiley & Sons, 1997:9-22
2. Gold R, Linington C, Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 Years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006;129:1953-71
3. Lassmann H. Experimental models of multiple sclerosis. Rev Neurol 2007;163:651-55 (Pubitemid 47015564)
4. Furlan R, Cuomo C, Martino G. Animal models of multiple sclerosis. Methods Mol Biol 2009;549:157-73
5. Sriram S, Steiner J. Experimental allergic encephalomyelitis: A misleading model of multiple sclerosis. Ann Neurol 2005;58:939-45
6. Fabis MJ, Scott GS, Kean RB, et al. Loss of blood-brain barrier integrity in the spinal cord is common to experimental allergic encephalomyelitis in knockout mouse models. Proc Natl Acad Sci USA 2007;104:5656-61
7. Stüve O, Kieseier BC, Hemmer B, et al. Translational research in neurology and neuroscience 2010: Multiple sclerosis. Arch Neurol 2010;67: 1307-15
8. Pfeiffer F, Schäfer J, Lyck R, et al. Claudin-1induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis. Acta Neuropathol 2011;122:601-14
9. Raine CS, Cannella B, Duijvestijn AM, et al. Homing to central nervous system vasculature by antigen-specific lymphocytes. II. Lymphocyte/endothelial cell adhesion during the initial stages of autoimmune demyelination. Lab Invest 1990;63:476-89
10. Shin T, Kojima T, Tanuma N, et al. The subarachnoid space as a site for precursor T cell proliferation and effector T cell selection in experimental autoimmune encephalomyelitis. J Neuroimmunol 1995;56:171-78
11. Benveniste EN. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med 1997;75: 165-73
12. Henderson AP, Barnett MH, Parratt JD, et al. Multiple sclerosis: Distribution of inflammatory cells in newly forming lesions. Ann Neurol 2009;66:739-53
13. Kermode AG, Thompson AJ, Tofts P, et al. Breakdown of the bloodbrain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis: Pathogenetic and clinical implications. Brain 1990; 113:1477-89
14. de Vries HE, Kuiper J, de Boer AG, et al. The blood-brain barrier in neuroinflammatory diseases. Pharmacol Rev 1997;49:143-55
15. Plumb J, McQuaid S, Mirakhur M, et al. Abnormal endothelial tight junctions in active lesions and normal-Appearing white matter in multiple sclerosis. Brain Pathol 2002;12:154-69
16. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005;57:173-85
17. Vos CM, Geurts JJ, Montagne L, et al. Blood-brain barrier alterations in both focal and diffuse abnormalities on postmortem MRI in multiple sclerosis. Neurobiol Dis 2005;20:953-60
18. Leech S, Kirk J, Plumb J, et al. Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis. Neuropathol Appl Neurobiol 2007;33:86-98
19. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008;57:178-201
20. McQuaid S, Cunnea P, McMahon J, et al. The effects of blood-brain barrier disruption on glial cell function in multiple sclerosis. Biochem Soc Trans 2009;37:329-31
21. Tysiak E, Asbach P, Aktas O, et al. Beyond blood brain barrier breakdownVIn vivo detection of occult neuroinflammatory foci by magnetic nanoparticles in high field MRI. J Neuroinflammation 2009;6:20
22. Weiss N, Miller F, Cazaubon S, et al. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 2009; 1788:842-57
23. Liebner S, Kniesel U, Kalbacher H, et al. Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur. J Cell Biol 2000;79:707-17
24. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Mol Cell Biol 2001;2:285-93
25. Wolburg H, Lippoldt A. The tight junctions of the blood-brain barrier: Development, composition and regulation. Vascul Pharmacol 2002;38: 323-37
26. Hirabayashi S, Hata Y. JAM family proteins: Tight junction proteins that belong to the immunoglobulin superfamily. In: Gonzales-Mariscal L, ed. Tight Junctions. New York: Springer, 2006:43-53
27. Abbott NJ, Patabendige AA, Dolman DE, et al. Structure and function of the blood-brain barrier. Neurobiol Dis 2010;37:13-25
28. Claudio L, Raine CS, Brosnan CF. Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis. Acta Neuropathol 1995;90:228-38
29. Kirk J, Plumb J, Mirakhur M, et al. Tight junctional abnormality in multiple sclerosis white matter affects all calibers of vessel and is associated with blood-brain barrier leakage and active demyelination. J Pathol 2003;201:319-27
30. McQuaid S, Kirk J. The blood-brain barrier in multiple sclerosis. Int Congress Series 2005;1277:235-43
31. van Horssen J, Bö L, Vos CM, et al. Basement membrane proteins in multiple sclerosisYassociated inflammatory cuffs: Potential role in influx and transport of leukocytes. J Neuropathol Exp Neurol 2005;64: 722-29
32. Wosik K, Cayrol R, Dodelet-Devillers A, et al. Angiotensin II controls occludin function and is required for blood brain barrier maintenance: Relevance to multiple sclerosis. J Neurosci 2007;27:9032-42
33. Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta 2011;812:252-64
34. Juhler M, Blasberg RG, Fenstermacher JD, et al. A spatial analysis of the blood-brain barrier damage in experimental allergic encephalomyelitis. J Cereb Blood Flow Metab 1985;5:545-53
35. Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler. 2003;9:540-9 (Pubitemid 37479401)
36. Xu S, Jordan EK, Brocke S, et al. Study of relapsing remitting experimental allergic encephalomyelitis SJL mouse model using MION-46L enhanced in vivo MRI: Early histopathological correlation. J Neurosci Res 1998;52:549-58
37. Wolburg H, Wolburg-Buchholz K, Kraus J, et al. Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol 2003;105:586-92
38. Floris S, Blezer EL, Schreibelt G, et al. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: A quantitative MRI study. Brain 2004;127:616-27
39. Morgan L, Shah B, Rivers LE, et al. Inflammation and dephosphorylation of the tight junction protein occludin in an experimental model of multiple sclerosis. Neuroscience 2007;147:664-73
40. Wolburg-Buchholz K, Mack AF, Steiner E, et al. Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol 2009,118: 219-33
41. Bennett J, Basivireddy J, Kollar A, et al. Blood-brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE. J Neuroimmunol 2010;229:180-91
42. Kidd D, Barkhof F, McConnell R, et al. Cortical lesions in multiple sclerosis. Brain 1999;122:17-26
43. Peterson JW, Bö L, Mörk S, et al. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 2001;50:389-400
44. BL L, Vedeler CA, Nyland H, et al. Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 2003;9:323-31
45. De Stefano N, Matthews PM, Filippi M, et al. Evidence of early cortical atrophy in MS: Relevance to white matter changes and disability. Neurology 2003;60:1157-6246
46. Bö L, Geurts JJ, van der Valk P, et al. Lack of correlation between cortical demyelination and white matter pathologic changes in multiple sclerosis. Arch Neurol 2007;64:76-80
47. Bö L, Geurts JJ, Mörk SJ, et al. Grey matter pathology in multiple sclerosis. Acta Neurol Scand Suppl 2006;183:48-50
48. Pirko I, Lucchinetti CF, Sriram S, et al. Gray matter involvement in multiple sclerosis. Neurology 2007;68:634-42
49. Stadelmann C, Albert M, Wegner C, et al. Cortical pathology in multiple sclerosis. Curr Opin Neurol 2008;21:229-34
50. BL L. The histopathology of grey matter demyelination in multiple sclerosis. Acta Neurol Scand Suppl 2009;189:51-57
51. Calabrese M, Agosta F, Rinaldi F, et al. Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 2009;66:1144-50
52. Geurts JJ, Stys PK, Minagar A, et al. Gray matter pathology in (chronic) MS: Modern views on an early observation. Neurol Sci 2009;282:12-20
53. Vercellino M, Masera S, Lorenzatti M, et al. Demyelination, inflammation, and neurodegeneration in multiple sclerosis deep gray matter. J Neuropathol Exp Neurol 2009;68:489-502
54. Wegner C, Stadelmann C. Gray matter pathology and multiple sclerosis. Curr Neurol Neurosci Rep 2009;9:399-404
55. Simon B, Schmidt S, Lukas C, et al. Improved in vivo detection of cortical lesions in multiple sclerosis using double inversion recovery MR imaging at 3 Tesla. Eur Radiol 2010;20:1675-83
56. van Horssen J, Brink BP, de Vries HE, et al. The blood-brain barrier in cortical multiple sclerosis lesions. J Neuropathol Exp Neurol 2007;66: 321-28
57. Pomeroy IM, Matthews PM, Frank JA, et al. Demyelinated neocortical lesions in marmoset autoimmune encephalomyelitis mimic those in multiple sclerosis. Brain 2005;128:2713-21
58. Merkler D, Ernsting T, Kerschensteiner M, et al. A new focal EAE model of cortical demyelination: Multiple sclerosis-like lesions with rapid resolution of inflammation and extensive remyelination. Brain 2006;129:1972-83
59. Storch MK, Bauer J, Linington C, et al. Cortical demyelination can be modeled in specific rat models of autoimmune encephalomyelitis and is major histocompatibility complex (MHC) haplotype-related. J Neuropathol Exp Neurol 2006;65:1137-42
60. Girolamo F, Ferrara G, Strippoli M, et al. Cerebral cortex demyelination and oligodendrocyte precursor response to experimental autoimmune encephalomyelitis. Neurobiol Dis 2011;43:678-89
61. Mangiardi M, Crawford DK, Xia X, et al. An animal model of cortical and callosal pathology in multiple sclerosis. Brain Pathol 2010;21: 263-78
62. Muller DM, Pender MP, Greer JM. Blood-brain barrier disruption and lesion localisation in experimental autoimmune encephalomyelitis with predominant cerebellar and brainstem involvement. J Neuroimmunol 2005;160:162-69
63. Kügler S, Böcker K, Heusipp G, et al. Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model. Cell Microbiol 2007;9:619-32
64. Stein VM, Baumgärtner W, Schröder S, et al. Differential expression of CD45 on canine microglial cells. J Vet Med A Physiol Pathol Clin Med 2007;54:314-20
65. Padden M, Leech S, Craig B, et al. Differences in expression of junctional adhesion molecule-A and beta-catenin in multiple sclerosis brain tissue: Increasing evidence for the role of tight junction pathology. Acta Neuropathol 2007;113:177-86
66. Alexander JS, Zivadinov R, Maghzi AH, et al. Multiple sclerosis and cerebral endothelial dysfunction: Mechanisms. Pathophysiology 2011; 18:3-12
67. Körner H, Sedgwick JD. Tumour necrosis factor and lymphotoxin: Molecular aspects and role in tissue-specific autoimmunity. Immunol Cell Biol 1996;74:465-72
68. Minagar A, Alexander S. Blood-brain barrier disruption in multiple sclerosis. Mult Scler 2003;9:540-49
69. Kim SU, de Vellis J. Microglia in health and disease. J Neurosci Res 2005;81:302-13
70. Kebir H, Kreymborg K, Ifergan I, et al. Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 2007;13:1173-75
71. Argaw AT, Gurfein BT, Zhang Y, et al. VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci USA 2009;106:1977-82
72. Capaldo CT, Nusrat A. Cytokine regulation of tight junctions. Biochim Biophys Acta 2009;1788:864-71
73. Simka M. Blood-brain barrier compromise with endothelial inflammation may lead to autoimmune loss of myelin during multiple sclerosis. Curr Neurovasc Res 2009;6:132-38
74. Coisne C, Engelhardt B. Tight junctions in brain barriers during central nervous system inflammation. Antioxid Redox Signal 2011;15:1285-303
75. van Horssen J, Witte ME, Schreibelt G, et al. Radical changes in multiple sclerosis pathogenesis. Biochim Biophys Acta 2011;1812:141-50
76. Hochmeister S, Grundtner R, Bauer J, et al. Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis. J Neuropathol Exp Neurol 2006;65:855-65
77. Ladewig G, Jestaedt L, Misselwitz B, et al. Spatial diversity of bloodbrain barrier alteration and macrophage invasion in experimental autoimmune encephalomyelitis: A comparative MRI study. Exp Neurol 2009; 220:207-11
78. van deer Valk P, Amor S. Preactive lesions in multiple sclerosis. Curr Opin Neurol 2009;22:207-13
79. Kooi EJ, Geurts JJ, van Horssen J, et al. Meningeal inflammation is not associated with cortical demyelination in chronic multiple sclerosis. J Neuropathol Exp Neurol 2009;68:1021-28
80. Bechmann I, Mor G, Nilsen J, et al. FasL (CD95L, Apo1L) is expressed in the normal rat and human brain: Evidence for the existence of an immunological brain barrier. Glia 1999;27:62-74
81. Aloisi F, Serafini B, Adorini L. Glia-T cell dialogue. J Neuroimmunol 2000;24:111-17
82. Bechmann I, Steiner B, Gimsa U, et al. Astrocyte-induced T cell elimination is CD95 ligand dependent. J Neuroimmunol 2002;132:60-65
83. Brink BP, Veerhuis R, Breij ECW, et al. The pathology of multiple sclerosis is location-dependent: No significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol 2005;64: 147-55
84. Heimark RL. Cell-cell adhesion of molecules the blood-brain barrier. In: Pardridge WM, ed. The Blood-Brain Barrier: Cellular and Molecular Biology. New York, NY: Lippincott-Raven, 1993:88-106
85. van Horssen J, Bö L, Dijkstra CD, et al. Extensive extracellular matrix depositions in active multiple sclerosis lesions. Neurobiol Dis 2006;24: 484-91
86. Wu C, Ivars F, Anderson P, et al. Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med 2009;15:519-27
87. Chun HB, Scott M, Niessen S, et al. The proteome of mouse brain microvessel membranes and basal lamina. J Cereb Blood Flow Metab 2001;31:2267-81
88. Greenwood J, Heasman SJ, Alvarez JI, et al. Review: Leukocyte-endothelial cell crosstalk at the blood-brain barrier: A prerequisite for successful immune cell entry to the brain. Neuropathol Appl Neurobiol 2011;37:24-39
89. Matter K, Balda MS. Occludin and the function of tight junctions. Int Rev Cytol 1999;186:117-46
90. Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: Nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol 2000;279:G851-57
91. Nitta T, Hata M, Gotoh S, et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 2003;161: 653-60
92. Erickson KK, Sundstrom JM, Antonetti DA. Vascular permeability in ocular disease and the role of tight junctions. Angiogenesis 2007;10: 103-17
93. Krause G, Winkler L, Mueller SL, et al. Structure and function of claudins. Biochim Biophys Acta 2008;1778:631-45
94. Lal-Nag M, Morin PJ. The claudins. Genome Biol 2009;10:235.1-7
95. Stamatovic SM, Keep RF, Andjelkovic AV. Brain endothelial cell-cell junctions: How to ''open'' the blood brain barrier. Curr Neuropharmacol 2008;6:179-92
96. Cardoso FL, Brites D, Brito MA. Looking at the blood-brain barrier: Molecular anatomy and possible investigation approaches. Brain Res Rev 2010;64:328-63
97. Virgintino D, Errede M, Robertson D, et al. Immunolocalization of tight junction proteins in the adult and developing human brain. Histochem Cell Biol 2004;122:51-59
98. Ivanov AI, Nusrat A, Parkos CA. Endocytosis of epithelial apical junctional proteins by a clathrin-mediated pathway into a unique storage compartment. Mol Biol Cell 2004;15:176-88
99. Ivanov AI, Nusrat A, Parkos CA. Endocytosis of the apical junctional complex: Mechanisms and possible roles in regulation of epithelial barriers. Bioessays 2005;27:356-65
100. Stamatovic SM, Keep RF, Wang MM, et al. Caveolae-mediated internalization of occludin and claudin-5 during CCL2-induced tight junction remodeling in brain endothelial cells. J Biol Chem 2009;284: 19053-66
101. Virgintino D, Robertson D, Errede M, et al. Expression of caveolin-1 in human brain microvessels. Neuroscience 2002;115:145-52
102. Song L, Ge S, Pachter JS. Caveolin-1 regulates expression of junctionassociated proteins in brain microvascular endothelial cells. Blood 2007; 109:1515-23
103. Dodelet-Devillers A, Cayrol R, van Horssen J, et al. Functions of lipid raft membrane microdomains at the blood-brain barrier. J Mo. Med 2009;87:765-74
104. Shin T, Kim H, Jin JK, et al. Expression of caveolin-1, -2, and -3 in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis. J Neuroimmunol 2005;165:11-20
105. Nag S, Venugopalan R, Stewart DJ. Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during bloodbrain barrier breakdown. Acta Neuropathol 2007;114:459-69
106. Zhong Y, Smart EJ, Weksler B, et al. Caveolin-1 regulates human immunodeficiency virus-1 Tat-induced alterations of tight junction protein expression via modulation of the Ras signaling. J Neurosci 2008;28: 7788-96
107. Beauchesne E, Desjardins P, Butterworth RF, et al. Up-regulation of caveolin-1 and blood-brain barrier breakdown are attenuated by N-Acetylcysteine in thiamine deficiency. Neurochem Int 2010;57:830-37
108. Marchiando AM, Shen L, Graham WV, et al. Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. J Cell Biol 2010;189:111-26
109. Terai T, Nishimura N, Kanda I, et al. JRAB/MICAL-L2 is a junctional Rab13-binding protein mediating the endocytic recycling of occludin. Mol Biol Cell 2006;17:2465-75
110. Virgintino D, Robertson D, Benagiano V, et al. Immunogold cytochemistry of the blood-brain barrier glucose transporter GLUT1 and endogenous albumin in the developing human brain. Brain Res Dev Brain Res 2000;123:95-101
111. Kirkham M, Parton RG. Clathrin-independent endocytosis: New insights into caveolae and noncaveolar lipid raft carriers. Biochim Biophys Acta 2005;1746:349-63
112. Piontek J, Winkler L, Wolburg H, et al. Formation of tight junction: Determinants of homophilic interaction between classic claudins. FASEB J 2008;22:146-58
113. Matsuda M, Kubo A, Furuse M, et al. A peculiar internalization of claudins, tight junction-specific adhesion molecules, during the intercellular movement of epithelial cells. J Cell Sci 2004;117:1247-57
114. Ravikumar B, Moreau K, Jahreiss L, et al. Plasma membrane contributes to the formation of preautophagosomal structures. Nat Cell Biol 2010;12:747-57
115. Florey O, Kim SE, Sandoval CP, et al. Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes. Nat Cell Biol 2011;13:1335-43
116. Han F, Chen YX, Lu YM, et al. Regulation of the ischemia-induced autophagy-lysosome processes by nitrosative stress in endothelial cells. J Pineal Res 2011;51:124-35
117. Kang R, Zeh HJ, Lotze MT, et al. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 2011;18:571-80
118. Trotter J, Karram K, Nishiyama A. NG2 cells: Properties, progeny and origin. Brain Res Rev 2010;63:72-82
119. Kuhlmann T, Miron V, Cui Q, et al. Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain 2008;131:1749-58
120. Stadelmann C, Brück W. Interplay between mechanisms of damage and repair in multiple sclerosis. J Neurol 2008;255:12-18
121. Wolswijk G, Noble M. Identification of an adult-specific glial progenitor cell. Development 1989;105:387-400
122. Nunes MC, Roy NS, Keyoung HM, et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 2003;9:439-47
123. Nishiyama A, Yang Z, Butt A. Astrocytes and NG2-glia: What's in a name? J Anat 2005;207:687-93
124. Buffo A, Rite I, Tripathi P, et al. Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc Natl Acad Sci USA 2008;105:3581-86
125. Kang SH, Fukaya M, Yang JK, et al. NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron 2010;68:668-81
126. Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006;7:41-53
127. Copray S, Huynh JL, Sher F, et al. Epigenetic mechanisms facilitating oligodendrocyte development, maturation, and aging. Glia 2009;57: 1579-87
128. Nishiyama A, Komitova M, Suzuki R, et al. Polydendrocytes (NG2 cells): Multifunctional cells with lineage plasticity. Nat Rev Neurosci 2009;10:9-22
129. Watzlawik J, Warrington AE, Rodriguez M. Importance of oligodendrocyte protection, BBB breakdown and inflammation for remyelination. Exp Rev Neurother 2010;10:441-57
130. Arai K, Lo EH. An oligovascular niche: Cerebral endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells. J Neurosci 2009;29:4351-55
131. Ozerdem U, Stallcup WB. Early contribution of pericytes to angiogenic sprouting and tube formation. Angiogenesis 2003;6241-49
132. Ozerdem U, Stallcup WB. Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan. Angiogenesis 2004;7: 269-76
133. Huang FJ, You WK, Bonaldo P, et al. Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse. Dev Biol 2010;344:1035-46
134. Tillet E, Gential B, Garrone R, et al. NG2 proteoglycan mediates beta1 integrin-independent cell adhesion and spreading on collagen VI. J Cell Biochem 2002;86:726-36
135. Engelhardt B. A1-Integrin/matrix interactions support blood-brain barrier integrity. J Cereb Blood Flow Metab 2011;31:1969-71