Biphasic mechanisms of neurovascular unit injury and protection in CNS diseases

CNS and Neurological Disorders - Drug Targets

Volumn 12, Issue 3, 2013, Pages 302-315

  Maki, Takakuni ^a   Hayakawa, Kazuhide ^a   Pham, Loc Duyen D ^a   Xing, Changhong ^a   Lo, Eng H ^a   Arai, Ken ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Astrocyte; Central nervous system injury; Cerebral endothelial cell; Microglia; Neuroprotection; Neurovascular unit; Remodeling; Stroke

Indexed keywords

ALPHA SYNUCLEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; CD4 ANTIGEN; CONNEXIN 30; CONNEXIN 43; COPPER ZINC SUPEROXIDE DISMUTASE; GAMMA INTERFERON; GELATINASE B; GLIAL FIBRILLARY ACIDIC PROTEIN; GLYPICAN; HIGH MOBILITY GROUP B1 PROTEIN; INTERLEUKIN 10; INTERLEUKIN 4; LIPOPOLYSACCHARIDE; MESSENGER RNA; NEUROTROPHIN 3; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; SMAD PROTEIN; THROMBOSPONDIN; TISSUE INHIBITOR OF METALLOPROTEINASE 3; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; ASTROCYTE; BLOOD BRAIN BARRIER; BLOOD VESSEL INJURY; BRAIN INJURY; CELL CULTURE; CELL INTERACTION; CELL MIGRATION; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM DISEASE; CEREBROVASCULAR ACCIDENT; DEGENERATIVE DISEASE; DISEASE COURSE; EXTRACELLULAR MATRIX; FRACTIONAL ANISOTROPY; HOMEOSTASIS; HUMAN; INFLAMMATION; MICROGLIA; MIDDLE CEREBRAL ARTERY OCCLUSION; MULTIINFARCT DEMENTIA; MULTIPLE SCLEROSIS; NERVE FIBER REGENERATION; NERVOUS SYSTEM INJURY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PATHOPHYSIOLOGY; PERICYTE; PROTEIN EXPRESSION;

CELL COMMUNICATION; CENTRAL NERVOUS SYSTEM DISEASES; ENDOTHELIAL CELLS; HUMANS; NERVE REGENERATION; NEUROGLIA; NEURONS;

EID: 84878654913     PISSN: 18715273     EISSN: 19963181     Source Type: Journal    
DOI: 10.2174/1871527311312030004     Document Type: Article

References (175)

1. Moskowitz, M.A.; Lo, E.H.; Iadecola, C. The science of stroke: mechanisms in search of treatments. Neuron, 2010, 67(2), 181-198.
2. Lok, J.; Gupta, P.; Guo, S.; Kim, W.J.; Whalen, M.J.; van Leyen, K.; Lo, E.H. Cell-cell signaling in the neurovascular unit. Neurochem. Res., 2007, 32(12), 2032-2045.
3. del Zoppo, G.J. Stroke and neurovascular protection. N. Engl. J. Med., 2006, 354(6), 553-555.
4. Zlokovic, B.V. Neurodegeneration and the neurovascular unit. Nat. Med., 2010, 16(12), 1370-1371.
5. Quaegebeur, A.; Lange, C.; Carmeliet, P. The neurovascular link in health and disease: molecular mechanisms and therapeutic implications. Neuron, 2011, 71(3), 406-424.
6. Zacchigna, S.; Lambrechts, D.; Carmeliet, P. Neurovascular signalling defects in neurodegeneration. Nat. Rev. Neurosci., 2008, 9(3), 169-181.
7. Iadecola, C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat. Rev. Neurosci., 2004, 5(5), 347-360.
8. Arai, K.; Lok, J.; Guo, S.; Hayakawa, K.; Xing, C.; Lo, E.H. Cellular mechanisms of neurovascular damage and repair after stroke. J. Child Neurol., 2011, 26(9), 1193-1198.
9. Urich, E.; Lazic, S.E.; Molnos, J.; Wells, I.; Freskgard, P.O. Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models. PLoS One, 2012, 7(5), e38149.
10. Olah, M.; Amor, S.; Brouwer, N.; Vinet, J.; Eggen, B.; Biber, K.; Boddeke, H.W. Identification of a microglia phenotype supportive of remyelination. Glia, 2012, 60(2), 306-321.
11. Zhang, Y.; Barres, B.A. Astrocyte heterogeneity: an underappreciated topic in neurobiology. Curr. Opin. Neurobiol., 2010, 20(5), 588-594.
12. Zamanian, J.L.; Xu, L.; Foo, L.C.; Nouri, N.; Zhou, L.; Giffard, R.G.; Barres, B.A. Genomic analysis of reactive astrogliosis. J. Neurosci., 2012, 32(18), 6391-6410.
13. Barres, B.A. The mystery and magic of glia: a perspective on their roles in health and disease. Neuron, 2008, 60(3), 430-440.
14. Allen, N.J.; Barres, B.A. Neuroscience: Glia-more than just brain glue. Nature, 2009, 457(7230), 675-677.
15. Lo, E.H. Degeneration and repair in central nervous system disease. Nat. Med., 2010, 16(11), 1205-1209.
16. Hermann, D.M.; Chopp, M. Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. Lancet Neurol., 2012, 11(4), 369-380.
17. Zhang, Z.G.; Chopp, M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol., 2009, 8(5), 491-500.
18. Lo, E.H. A new penumbra: transitioning from injury into repair after stroke. Nat. Med., 2008, 14(5), 497-500.
19. Arai, K.; Jin, G.; Navaratna, D.; Lo, E.H. Brain angiogenesis in developmental and pathological processes: neurovascular injury and angiogenic recovery after stroke. FEBS J., 2009, 276(17), 4644-4652.
20. Iadecola, C.; Anrather, J. The immunology of stroke: from mechanisms to translation. Nat. Med., 2011, 17(7), 796-808.
21. Xing, C.; Hayakawa, K.; Lok, J.; Arai, K.; Lo, E.H. Injury and repair in the neurovascular unit. Neurol. Res., 2012, 34(4), 325-330.
22. Nedergaard, M.; Ransom, B.; Goldman, S.A. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci., 2003, 26(10), 523-530.
23. Pfrieger, F.W.; Barres, B.A. Synaptic efficacy enhanced by glial cells in vitro. Science, 1997, 277(5332), 1684-1687.
24. Christopherson, K.S.; Ullian, E.M.; Stokes, C.C.; Mullowney, C.E.; Hell, J.W.; Agah, A.; Lawler, J.; Mosher, D.F.; Bornstein, P.; Barres, B.A. Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell, 2005, 120(3), 421-433.
25. Mauch, D.H.; Nagler, K.; Schumacher, S.; Goritz, C.; Muller, E.C.; Otto, A.; Pfrieger, F.W. CNS synaptogenesis promoted by gliaderived cholesterol. Science, 2001, 294(5545), 1354-1357.
26. Allen, N.J.; Bennett, M.L.; Foo, L.C.; Wang, G.X.; Chakraborty, C.; Smith, S.J.; Barres, B.A. Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature, 2012, 486(7403), 410-414.
27. Iadecola, C.; Nedergaard, M. Glial regulation of the cerebral microvasculature. Nat. Neurosci., 2007, 10(11), 1369-1376.
28. Eroglu, C.; Barres, B.A. Regulation of synaptic connectivity by glia. Nature, 2010, 468(7321), 223-231.
29. Bush, T.G.; Puvanachandra, N.; Horner, C.H.; Polito, A.; Ostenfeld, T.; Svendsen, C.N.; Mucke, L.; Johnson, M.H.; Sofroniew, M.V. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron, 1999, 23(2), 297-308.
30. Argaw, A.T.; Asp, L.; Zhang, J.; Navrazhina, K.; Pham, T.; Mariani, J.N.; Mahase, S.; Dutta, D.J.; Seto, J.; Kramer, E.G.; Ferrara, N.; Sofroniew, M.V.; John, G.R. Astrocyte-derived VEGFA drives blood-brain barrier disruption in CNS inflammatory disease. J. Clin. Invest., 2012, 122(7), 2454-2468.
31. Ricci, G.; Volpi, L.; Pasquali, L.; Petrozzi, L.; Siciliano, G. Astrocyte-neuron interactions in neurological disorders. J. Biol. Phys., 2009, 35(4), 317-336.
32. Arai, K.; Lo, E.H. Astrocytes protect oligodendrocyte precursor cells via MEK/ERK and PI3K/Akt signaling. J. Neurosci. Res., 2010, 88(4), 758-763.
33. Moore, C.S.; Abdullah, S.L.; Brown, A.; Arulpragasam, A.; Crocker, S.J. How factors secreted from astrocytes impact myelin repair. J. Neurosci. Res., 2011, 89(1), 13-21.
34. Hayakawa, K.; Pham, L.D.; Katusic, Z.S.; Arai, K.; Lo, E.H. Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery. Proc. Natl. Acad. Sci. USA, 2012, 109(19), 7505-7510.
35. Giaume, C.; Koulakoff, A.; Roux, L.; Holcman, D.; Rouach, N. Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat. Rev. Neurosci., 2010, 11(2), 87-99.
36. Chew, S.S.; Johnson, C.S.; Green, C.R.; Danesh-Meyer, H.V. Role of connexin43 in central nervous system injury. Exp. Neurol., 2010, 225(2), 250-261.
37. Fitch, M.T.; Silver, J. CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp. Neurol., 2008, 209(2), 294-301.
38. Silver, J.; Miller, J.H. Regeneration beyond the glial scar. Nat. Rev. Neurosci., 2004, 5(2), 146-156.
39. Abbott, N.J.; Ronnback, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci., 2006, 7(1), 41-53.
40. Myer, D.J.; Gurkoff, G.G.; Lee, S.M.; Hovda, D.A.; Sofroniew, M.V. Essential protective roles of reactive astrocytes in traumatic brain injury. Brain, 2006, 129(Pt 10), 2761-2772.
41. Xin, H.; Li, Y.; Shen, L.H.; Liu, X.; Wang, X.; Zhang, J.; Pourabdollah-Nejad, D.S.; Zhang, C.; Zhang, L.; Jiang, H.; Zhang, Z.G.; Chopp, M. Increasing tPA activity in astrocytes induced by multipotent mesenchymal stromal cells facilitate neurite outgrowth after stroke in the mouse. PLoS One, 2010, 5(2), e9027.
42. Cahoy, J.D.; Emery, B.; Kaushal, A.; Foo, L.C.; Zamanian, J.L.; Christopherson, K.S.; Xing, Y.; Lubischer, J.L.; Krieg, P.A.; Krupenko, S.A.; Thompson, W.J.; Barres, B.A. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci., 2008, 28(1), 264-278.
43. Doyle, J.P.; Dougherty, J.D.; Heiman, M.; Schmidt, E.F.; Stevens, T.R.; Ma, G.; Bupp, S.; Shrestha, P.; Shah, R.D.; Doughty, M.L.; Gong, S.; Greengard, P.; Heintz, N. Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell, 2008, 135(4), 749-762.
44. Takata, N.; Hirase, H. Cortical layer 1 and layer 2/3 astrocytes exhibit distinct calcium dynamics in vivo. PLoS One, 2008, 3(6), e2525.
45. Zlokovic, B.V. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron, 2008, 57(2), 178-201.
46. Zlokovic, B.V. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat. Rev. Neurosci., 2011, 12(12), 723-738.
47. Bell, R.D.; Winkler, E.A.; Sagare, A.P.; Singh, I.; LaRue, B.; Deane, R.; Zlokovic, B.V. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron, 2010, 68(3), 409-427.
48. Makita, T.; Sucov, H.M.; Gariepy, C.E.; Yanagisawa, M.; Ginty, D.D. Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons. Nature, 2008, 452(7188), 759-763.
49. Dugas, J.C.; Mandemakers, W.; Rogers, M.; Ibrahim, A.; Daneman, R.; Barres, B.A. A novel purification method for CNS projection neurons leads to the identification of brain vascular cells as a source of trophic support for corticospinal motor neurons. J. Neurosci., 2008, 28(33), 8294-8305.
50. Guo, S.; Kim, W.J.; Lok, J.; Lee, S.R.; Besancon, E.; Luo, B.H.; Stins, M.F.; Wang, X.; Dedhar, S.; Lo, E.H. Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc. Natl. Acad. Sci. USA, 2008, 105(21), 7582-7587.
51. Ohab, J.J.; Fleming, S.; Blesch, A.; Carmichael, S.T. A neurovascular niche for neurogenesis after stroke. J. Neurosci., 2006, 26(50), 13007-13016.
52. Kokovay, E.; Goderie, S.; Wang, Y.; Lotz, S.; Lin, G.; Sun, Y.; Roysam, B.; Shen, Q.; Temple, S. Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell, 2010, 7(2), 163-173.
53. Arai, K.; Lo, E.H. Oligovascular signaling in white matter stroke. Biol. Pharm. Bull., 2009, 32(10), 1639-1644.
54. Arai, K.; Lo, E.H. An oligovascular niche: cerebral endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells. J. Neurosci., 2009, 29(14), 4351-4355.
55. Hayakawa, K.; Seo, J.H.; Pham, L.D.; Miyamoto, N.; Som, A.T.; Guo, S.; Kim, K.W.; Lo, E.H.; Arai, K. Cerebral endothelial derived vascular endothelial growth factor promotes the migration but not the proliferation of oligodendrocyte precursor cells in vitro. Neurosci. Lett., 2012.
56. Hayakawa, K.; Pham, L.D.; Som, A.T.; Lee, B.J.; Guo, S.; Lo, E.H.; Arai, K. Vascular endothelial growth factor regulates the migration of oligodendrocyte precursor cells. J. Neurosci., 2011, 31(29), 10666-10670.
57. Menn, B.; Garcia-Verdugo, J.M.; Yaschine, C.; Gonzalez-Perez, O.; Rowitch, D.; Alvarez-Buylla, A. Origin of oligodendrocytes in the subventricular zone of the adult brain. J. Neurosci., 2006, 26(30), 7907-7918.
58. Paus, T.; Zijdenbos, A.; Worsley, K.; Collins, D.L.; Blumenthal, J.; Giedd, J.N.; Rapoport, J.L.; Evans, A.C. Structural maturation of neural pathways in children and adolescents: in vivo study. Science, 1999, 283(5409), 1908-1911.
59. Scholz, J.; Klein, M.C.; Behrens, T.E.; Johansen-Berg, H. Training induces changes in white-matter architecture. Nat. Neurosci., 2009, 12(11), 1370-1371.
60. Juraska, J.M.; Kopcik, J.R. Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Res., 1988, 450(1-2), 1-8.
61. Levine, J.M.; Reynolds, R.; Fawcett, J.W. The oligodendrocyte precursor cell in health and disease. Trends Neurosci., 2001, 24(1), 39-47.
62. Franklin, R.J.; Ffrench-Constant, C. Remyelination in the CNS: from biology to therapy. Nat. Rev. Neurosci., 2008, 9(11), 839-855.
63. Emery, B. Regulation of oligodendrocyte differentiation and myelination. Science, 2010, 330(6005), 779-782.
64. Griffiths, I.; Klugmann, M.; Anderson, T.; Yool, D.; Thomson, C.; Schwab, M.H.; Schneider, A.; Zimmermann, F.; McCulloch, M.; Nadon, N.; Nave, K.A. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science, 1998, 280(5369), 1610-1613.
65. Lappe-Siefke, C.; Goebbels, S.; Gravel, M.; Nicksch, E.; Lee, J.; Braun, P.E.; Griffiths, I.R.; Nave, K.A. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat. Genet., 2003, 33(3), 366-374.
66. Funfschilling, U.; Supplie, L.M.; Mahad, D.; Boretius, S.; Saab, A.S.; Edgar, J.; Brinkmann, B.G.; Kassmann, C.M.; Tzvetanova, I.D.; Mobius, W.; Diaz, F.; Meijer, D.; Suter, U.; Hamprecht, B.; Sereda, M.W.; Moraes, C.T.; Frahm, J.; Goebbels, S.; Nave, K.A. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature, 2012, 485(7399), 517-521.
67. Lee, Y.; Morrison, B.M.; Li, Y.; Lengacher, S.; Farah, M.H.; Hoffman, P.N.; Liu, Y.; Tsingalia, A.; Jin, L.; Zhang, P.W.; Pellerin, L.; Magistretti, P.J.; Rothstein, J.D. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature, 2012, 487(7408), 443-448.
68. Wilkins, A.; Majed, H.; Layfield, R.; Compston, A.; Chandran, S. Oligodendrocytes promote neuronal survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocytederived glial cell line-derived neurotrophic factor. J. Neurosci., 2003, 23(12), 4967-4974.
69. Wang, S.; Sdrulla, A.D.; diSibio, G.; Bush, G.; Nofziger, D.; Hicks, C.; Weinmaster, G.; Barres, B.A. Notch receptor activation inhibits oligodendrocyte differentiation. Neuron, 1998, 21(1), 63-75.
70. Charles, P.; Hernandez, M.P.; Stankoff, B.; Aigrot, M.S.; Colin, C.; Rougon, G.; Zalc, B.; Lubetzki, C. Negative regulation of central nervous system myelination by polysialylated-neural cell adhesion molecule. Proc. Natl. Acad. Sci. USA, 2000, 97(13), 7585-7590.
71. Mi, S.; Miller, R.H.; Lee, X.; Scott, M.L.; Shulag-Morskaya, S.; Shao, Z.; Chang, J.; Thill, G.; Levesque, M.; Zhang, M.; Hession, C.; Sah, D.; Trapp, B.; He, Z.; Jung, V.; McCoy, J.M.; Pepinsky, R.B. LINGO-1 negatively regulates myelination by oligodendrocytes. Nat. Neurosci., 2005, 8(6), 745-751.
72. Etxeberria, A.; Mangin, J.M.; Aguirre, A.; Gallo, V. Adult-born SVZ progenitors receive transient synapses during remyelination in corpus callosum. Nat. Neurosci., 2010, 13(3), 287-289.
73. Pham, L.D.; Hayakawa, K.; Seo, J.H.; Nguyen, M.N.; Som, A.T.; Lee, B.J.; Guo, S.; Kim, K.W.; Lo, E.H.; Arai, K. Crosstalk between oligodendrocytes and cerebral endothelium contributes to vascular remodeling after white matter injury. Glia, 2012, 60(6), 875-881.
74. Graeber, M.B. Changing face of microglia. Science, 2010, 330(6005), 783-788.
75. Hanisch, U.K.; Kettenmann, H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci., 2007, 10(11), 1387-1394.
76. Nimmerjahn, A.; Kirchhoff, F.; Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science, 2005, 308(5726), 1314-1318.
77. Davalos, D.; Grutzendler, J.; Yang, G.; Kim, J.V.; Zuo, Y.; Jung, S.; Littman, D.R.; Dustin, M.L.; Gan, W.B. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci., 2005, 8(6), 752-758.
78. Hughes, V. Microglia: The constant gardeners. Nature, 2012, 485(7400), 570-572.
79. Binstadt, B.A.; Patel, P.R.; Alencar, H.; Nigrovic, P.A.; Lee, D.M.; Mahmood, U.; Weissleder, R.; Mathis, D.; Benoist, C. Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat. Immunol., 2006, 7(3), 284-292.
80. Ren, L.; Lubrich, B.; Biber, K.; Gebicke-Haerter, P.J. Differential expression of inflammatory mediators in rat microglia cultured from different brain regions. Brain Res. Mol. Brain Res., 1999, 65(2), 198-205.
81. Batchelor, P.E.; Liberatore, G.T.; Wong, J.Y.; Porritt, M.J.; Frerichs, F.; Donnan, G.A.; Howells, D.W. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J. Neurosci., 1999, 19(5), 1708-1716.
82. Narantuya, D.; Nagai, A.; Sheikh, A.M.; Masuda, J.; Kobayashi, S.; Yamaguchi, S.; Kim, S.U. Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement. PLoS One, 2010, 5(7), e11746.
83. Michelucci, A.; Heurtaux, T.; Grandbarbe, L.; Morga, E.; Heuschling, P. Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: Effects of oligomeric and fibrillar amyloid-beta. J. Neuroimmunol., 2009, 210(1-2), 3-12.
84. Napoli, I.; Neumann, H. Protective effects of microglia in multiple sclerosis. Exp. Neurol., 2010, 225(1), 24-28.
85. Olah, M.; Ping, G.; De Haas, A.H.; Brouwer, N.; Meerlo, P.; Van Der Zee, E.A.; Biber, K.; Boddeke, H.W. Enhanced hippocampal neurogenesis in the absence of microglia T cell interaction and microglia activation in the murine running wheel model. Glia, 2009, 57(10), 1046-1061.
86. Mosser, D.M.; Edwards, J.P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol., 2008, 8(12), 958-969.
87. Armulik, A.; Genove, G.; Mae, M.; Nisancioglu, M.H.; Wallgard, E.; Niaudet, C.; He, L.; Norlin, J.; Lindblom, P.; Strittmatter, K.; Johansson, B.R.; Betsholtz, C. Pericytes regulate the blood-brain barrier. Nature, 2010, 468(7323), 557-561.
88. Daneman, R.; Zhou, L.; Kebede, A.A.; Barres, B.A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature, 2010, 468(7323), 562-566.
89. Peppiatt, C.M.; Howarth, C.; Mobbs, P.; Attwell, D. Bidirectional control of CNS capillary diameter by pericytes. Nature, 2006, 443(7112), 700-704.
90. Sa-Pereira, I.; Brites, D.; Brito, M.A. Neurovascular unit: a focus on pericytes. Mol. Neurobiol., 2012, 45(2), 327-347.
91. Mathiisen, T.M.; Lehre, K.P.; Danbolt, N.C.; Ottersen, O.P. The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia, 2010, 58(9), 1094-1103.
92. Sims, D.E. The pericyte--a review. Tissue Cell, 1986, 18(2), 153-174.
93. Armulik, A.; Genove, G.; Betsholtz, C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell, 2011, 21(2), 193-215.
94. Winkler, E.A.; Bell, R.D.; Zlokovic, B.V. Central nervous system pericytes in health and disease. Nat. Neurosci., 2011, 14(11), 1398-1405.
95. Gaengel, K.; Genove, G.; Armulik, A.; Betsholtz, C. Endothelialmural cell signaling in vascular development and angiogenesis. Arterioscler. Thromb. Vasc. Biol., 2009, 29(5), 630-638.
96. Candelario-Jalil, E.; Yang, Y.; Rosenberg, G.A. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience, 2009, 158(3), 983-994.
97. Virgintino, D.; Girolamo, F.; Errede, M.; Capobianco, C.; Robertson, D.; Stallcup, W.B.; Perris, R.; Roncali, L. An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis. Angiogenesis, 2007, 10(1), 35-45.
98. Darland, D.C.; Massingham, L.J.; Smith, S.R.; Piek, E.; Saint-Geniez, M.; D'Amore, P.A. Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival. Dev. Biol., 2003, 264(1), 275-288.
99. Donnan, G.A.; Fisher, M.; Macleod, M.; Davis, S.M. Stroke. Lancet, 2008, 371(9624), 1612-1623.
100. Macrez, R.; Ali, C.; Toutirais, O.; Le Mauff, B.; Defer, G.; Dirnagl, U.; Vivien, D. Stroke and the immune system: from pathophysiology to new therapeutic strategies. Lancet Neurol., 2011, 10(5), 471-480.
101. Chen, G.Y.; Nunez, G. Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol., 2010, 10(12), 826-837.
102. Hayakawa, K.; Qiu, J.; Lo, E.H. Biphasic actions of HMGB1 signaling in inflammation and recovery after stroke. Ann. NY Acad. Sci., 2010, 1207, 50-57.
103. Ikonomidou, C.; Turski, L. Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol., 2002, 1(6), 383-386.
104. Rosell, A.; Lo, E.H. Multiphasic roles for matrix metalloproteinases after stroke. Curr. Opin. Pharmacol., 2008, 8(1), 82-89.
105. Zhao, B.Q.; Wang, S.; Kim, H.Y.; Storrie, H.; Rosen, B.R.; Mooney, D.J.; Wang, X.; Lo, E.H. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat. Med., 2006, 12(4), 441-445.
106. Krupinski, J.; Kaluza, J.; Kumar, P.; Kumar, S.; Wang, J.M. Some remarks on the growth-rate and angiogenesis of microvessels in ischemic stroke. Morphometric and immunocytochemical studies. Patologia Polska, 1993, 44(4), 203-209.
107. Krupinski, J.; Kaluza, J.; Kumar, P.; Kumar, S.; Wang, J.M. Role of angiogenesis in patients with cerebral ischemic stroke. Stroke, 1994, 25(9), 1794-1798.
108. Szpak, G.M.; Lechowicz, W.; Lewandowska, E.; Bertrand, E.; Wierzba-Bobrowicz, T.; Dymecki, J. Border zone neovascularization in cerebral ischemic infarct. Folia Neuropathol., 1999, 37(4), 264-268.
109. Greenberg, D.A. Neurogenesis and stroke. CNS Neurol. Disord. Drug Targets, 2007, 6(5), 321-325.
110. Leys, D.; Henon, H.; Mackowiak-Cordoliani, M.A.; Pasquier, F. Poststroke dementia. Lancet Neurol., 2005, 4(11), 752-759.
111. Mena, H.; Cadavid, D.; Rushing, E.J. Human cerebral infarct: a proposed histopathologic classification based on 137 cases. Acta Neuropathol., 2004, 108(6), 524-530.
112. Yilmaz, A.; Fuchs, T.; Dietel, B.; Altendorf, R.; Cicha, I.; Stumpf, C.; Schellinger, P.D.; Blumcke, I.; Schwab, S.; Daniel, W.G.; Garlichs, C.D.; Kollmar, R. Transient decrease in circulating dendritic cell precursors after acute stroke: potential recruitment into the brain. Clin. Sci., 2010, 118(2), 147-157.
113. Zhang, R.; Zhang, Z.; Wang, L.; Wang, Y.; Gousev, A.; Zhang, L.; Ho, K.L.; Morshead, C.; Chopp, M. Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats. J. Cereb. Blood Flow Metab., 2004, 24(4), 441-448.
114. Zhang, R.L.; Zhang, Z.G.; Lu, M.; Wang, Y.; Yang, J.J.; Chopp, M. Reduction of the cell cycle length by decreasing G1 phase and cell cycle reentry expand neuronal progenitor cells in the subventricular zone of adult rat after stroke. J. Cereb. Blood Flow Metab., 2006, 26(6), 857-863.
115. Zhang, Z.G.; Zhang, L.; Tsang, W.; Soltanian-Zadeh, H.; Morris, D.; Zhang, R.; Goussev, A.; Powers, C.; Yeich, T.; Chopp, M. Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. J. Cereb. Blood Flow Metab., 2002, 22(4), 379-392.
116. Chopp, M.; Zhang, Z.G.; Jiang, Q. Neurogenesis, angiogenesis, and MRI indices of functional recovery from stroke. Stroke, 2007, 38(2 Suppl), 827-831.
117. Chopp, M.; Li, Y.; Zhang, J. Plasticity and remodeling of brain. J. Neurol. Sci., 2008, 265(1-2), 97-101.
118. Thored, P.; Wood, J.; Arvidsson, A.; Cammenga, J.; Kokaia, Z.; Lindvall, O. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke. Stroke, 2007, 38(11), 3032-3039.
119. Fagan, S.C.; Hess, D.C.; Hohnadel, E.J.; Pollock, D.M.; Ergul, A. Targets for vascular protection after acute ischemic stroke. Stroke, 2004, 35(9), 2220-2225.
120. Hansen, T.M.; Moss, A.J.; Brindle, N.P. Vascular endothelial growth factor and angiopoietins in neurovascular regeneration and protection following stroke. Curr. Neurovasc. Res., 2008, 5(4), 236-245.
121. Zhang, Z.G.; Zhang, L.; Jiang, Q.; Zhang, R.; Davies, K.; Powers, C.; Bruggen, N.; Chopp, M. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J. Clin. Invest., 2000, 106(7), 829-838.
122. Walsh, D.M.; Klyubin, I.; Fadeeva, J.V.; Cullen, W.K.; Anwyl, R.; Wolfe, M.S.; Rowan, M.J.; Selkoe, D.J. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature, 2002, 416(6880), 535-539.
123. Kalaria, R.N.; Akinyemi, R.; Ihara, M. Does vascular pathology contribute to Alzheimer changes? J. Neurol. Sci., 2012, 322(1-2), 141-147.
124. Weller, R.O.; Subash, M.; Preston, S.D.; Mazanti, I.; Carare, R.O. Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol., 2008, 18(2), 253-266.
125. Bell, R.D.; Deane, R.; Chow, N.; Long, X.; Sagare, A.; Singh, I.; Streb, J.W.; Guo, H.; Rubio, A.; Van Nostrand, W.; Miano, J.M.; Zlokovic, B.V. SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat. Cell Biol., 2009, 11(2), 143-153.
126. Zlokovic, B.V. Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci., 2005, 28(4), 202-208.
127. Bell, R.D.; Winkler, E.A.; Singh, I.; Sagare, A.P.; Deane, R.; Wu, Z.; Holtzman, D.M.; Betsholtz, C.; Armulik, A.; Sallstrom, J.; Berk, B.C.; Zlokovic, B.V. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature, 2012, 485(7399), 512-516.
128. Miao, J.; Xu, F.; Davis, J.; Otte-Holler, I.; Verbeek, M.M.; Van Nostrand, W.E. Cerebral microvascular amyloid beta protein deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant amyloid beta precursor protein. Am. J. Pathol., 2005, 167(2), 505-515.
129. Wyss-Coray, T.; Loike, J.D.; Brionne, T.C.; Lu, E.; Anankov, R.; Yan, F.; Silverstein, S.C.; Husemann, J. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat. Med., 2003, 9(4), 453-457.
130. Allaman, I.; Gavillet, M.; Belanger, M.; Laroche, T.; Viertl, D.; Lashuel, H.A.; Magistretti, P.J. Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability. J. Neurosci., 2010, 30(9), 3326-3338.
131. Naert, G.; Rivest, S. Hematopoietic CC-chemokine receptor 2 (CCR2) competent cells are protective for the cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease. Mol. Med., 2012, 18(1), 297-313.
132. Rogers, J.; Strohmeyer, R.; Kovelowski, C.J.; Li, R. Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide. Glia, 2002, 40(2), 260-269.
133. Takata, K.; Kitamura, Y.; Yanagisawa, D.; Morikawa, S.; Morita, M.; Inubushi, T.; Tsuchiya, D.; Chishiro, S.; Saeki, M.; Taniguchi, T.; Shimohama, S.; Tooyama, I. Microglial transplantation increases amyloid-beta clearance in Alzheimer model rats. FEBS Lett., 2007, 581(3), 475-478.
134. Hickman, S.E.; Allison, E.K.; El Khoury, J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J. Neurosci., 2008, 28(33), 8354-8360.
135. Haughey, N.J.; Nath, A.; Chan, S.L.; Borchard, A.C.; Rao, M.S.; Mattson, M.P. Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease. J. Neurochem., 2002, 83(6), 1509-1524.
136. Mu, Y.; Gage, F.H. Adult hippocampal neurogenesis and its role in Alzheimer's disease. Mol. Neurodegener., 2011, 6, 85.
137. Cantara, S.; Donnini, S.; Morbidelli, L.; Giachetti, A.; Schulz, R.; Memo, M.; Ziche, M. Physiological levels of amyloid peptides stimulate the angiogenic response through FGF-2. FASEB. J., 2004, 18(15), 1943-1945.
138. Abramov, E.; Dolev, I.; Fogel, H.; Ciccotosto, G.D.; Ruff, E.; Slutsky, I. Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat. Neurosci., 2009, 12(12), 1567-1576.
139. Hayashi, S.; Sato, N.; Yamamoto, A.; Ikegame, Y.; Nakashima, S.; Ogihara, T.; Morishita, R. Alzheimer disease-associated peptide, amyloid beta40, inhibits vascular regeneration with induction of endothelial autophagy. Arterioscler. Thromb. Vasc. Biol., 2009, 29(11), 1909-1915.
140. Lee, S.T.; Chu, K.; Jung, K.H.; Park, H.K.; Kim, D.H.; Bahn, J.J.; Kim, J.H.; Oh, M.J.; Lee, S.K.; Kim, M.; Roh, J.K. Reduced circulating angiogenic cells in Alzheimer disease. Neurology, 2009, 72(21), 1858-1863.
141. Meyer, E.P.; Ulmann-Schuler, A.; Staufenbiel, M.; Krucker, T. Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease. Proc. Natl. Acad. Sci. USA, 2008, 105(9), 3587-3592.
142. Pimentel-Coelho, P.M.; Rivest, S. The early contribution of cerebrovascular factors to the pathogenesis of Alzheimer's disease. Eur. J. Neurosci., 2012, 35(12), 1917-1937.
143. Obeso, J.A.; Rodriguez-Oroz, M.C.; Goetz, C.G.; Marin, C.; Kordower, J.H.; Rodriguez, M.; Hirsch, E.C.; Farrer, M.; Schapira, A.H.; Halliday, G. Missing pieces in the Parkinson's disease puzzle. Nat. Med., 2010, 16(6), 653-661.
144. McGeer, P.L.; McGeer, E.G. Glial reactions in Parkinson's disease. Mov. Disord., 2008, 23(4), 474-483.
145. Croisier, E.; Moran, L.B.; Dexter, D.T.; Pearce, R.K.; Graeber, M.B. Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition. J. Neuroinflammation, 2005, 2, 14.
146. Meredith, G.E.; Sonsalla, P.K.; Chesselet, M.F. Animal models of Parkinson's disease progression. Acta Neuropathol., 2008, 115(4), 385-398.
147. Yamanaka, K.; Chun, S.J.; Boillee, S.; Fujimori-Tonou, N.; Yamashita, H.; Gutmann, D.H.; Takahashi, R.; Misawa, H.; Cleveland, D.W. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci., 2008, 11(3), 251-253.
148. Saavedra, A.; Baltazar, G.; Santos, P.; Carvalho, C.M.; Duarte, E.P. Selective injury to dopaminergic neurons up-regulates GDNF in substantia nigra postnatal cell cultures: role of neuron-glia crosstalk. Neurobiol. Dis., 2006, 23(3), 533-542.
149. Marques, O.; Outeiro, T.F. Alpha-synuclein: from secretion to dysfunction and death. Cell Death Dis., 2012, 3(e350.
150. Dauer, W.; Przedborski, S. Parkinson's disease: mechanisms and models. Neuron, 2003, 39(6), 889-909.
151. Lee, J.; Zhu, W.M.; Stanic, D.; Finkelstein, D.I.; Horne, M.H.; Henderson, J.; Lawrence, A.J.; O'Connor, L.; Tomas, D.; Drago, J.; Horne, M.K. Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia. Brain, 2008, 131(Pt 6), 1574-1587.
152. Wada, K.; Arai, H.; Takanashi, M.; Fukae, J.; Oizumi, H.; Yasuda, T.; Mizuno, Y.; Mochizuki, H. Expression levels of vascular endothelial growth factor and its receptors in Parkinson's disease. Neuroreport, 2006, 17(7), 705-709.
153. Ohlin, K.E.; Francardo, V.; Lindgren, H.S.; Sillivan, S.E.; O'Sullivan, S.S.; Luksik, A.S.; Vassoler, F.M.; Lees, A.J.; Konradi, C.; Cenci, M.A. Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia. Brain, 2011, 134(Pt 8), 2339-2357.
154. Garbuzova-Davis, S.; Rodrigues, M.C.; Hernandez-Ontiveros, D.G.; Louis, M.K.; Willing, A.E.; Borlongan, C.V.; Sanberg, P.R. Amyotrophic lateral sclerosis: a neurovascular disease. Brain Res., 2011, 1398, 113-125.
155. Philips, T.; Robberecht, W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol., 2011, 10(3), 253-263.
156. Alexianu, M.E.; Kozovska, M.; Appel, S.H. Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology, 2001, 57(7), 1282-1289.
157. Lino, M.M.; Schneider, C.; Caroni, P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J. Neurosci., 2002, 22(12), 4825-4832.
158. Beers, D.R.; Henkel, J.S.; Xiao, Q.; Zhao, W.; Wang, J.; Yen, A.A.; Siklos, L.; McKercher, S.R.; Appel, S.H. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA, 2006, 103(43), 16021-16026.
159. Gong, Y.H.; Parsadanian, A.S.; Andreeva, A.; Snider, W.D.; Elliott, J.L. Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J. Neurosci., 2000, 20(2), 660-665.
160. Engelhardt, J.I.; Tajti, J.; Appel, S.H. Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch. Neurol., 1993, 50(1), 30-36.
161. Beers, D.R.; Henkel, J.S.; Zhao, W.; Wang, J.; Appel, S.H. CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc. Natl. Acad. Sci. USA, 2008, 105(40), 15558-15563.
162. Kang, S.H.; Fukaya, M.; Yang, J.K.; Rothstein, J.D.; Bergles, D.E. NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration. Neuron, 2010, 68(4), 668-681.
163. Seilhean, D.; Cazeneuve, C.; Thuries, V.; Russaouen, O.; Millecamps, S.; Salachas, F.; Meininger, V.; Leguern, E.; Duyckaerts, C. Accumulation of TDP-43 and alpha-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation. Acta Neuropathol., 2009, 118(4), 561-573.
164. Glass, C.K.; Saijo, K.; Winner, B.; Marchetto, M.C.; Gage, F.H. Mechanisms underlying inflammation in neurodegeneration. Cell, 2010, 140(6), 918-934.
165. Zhong, Z.; Deane, R.; Ali, Z.; Parisi, M.; Shapovalov, Y.; O'Banion, M.K.; Stojanovic, K.; Sagare, A.; Boillee, S.; Cleveland, D.W.; Zlokovic, B.V. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat. Neurosci., 2008, 11(4), 420-422.
166. Winkler, E.A.; Sengillo, J.D.; Bell, R.D.; Wang, J.; Zlokovic, B.V. Blood-spinal cord barrier pericyte reductions contribute to increased capillary permeability. J. Cereb. Blood Flow Metab., 2012, 32(10), 1841-1852.
167. Henkel, J.S.; Beers, D.R.; Wen, S.; Bowser, R.; Appel, S.H. Decreased mRNA expression of tight junction proteins in lumbar spinal cords of patients with ALS. Neurology, 2009, 72(18), 1614-1616.
168. Rule, R.R.; Schuff, N.; Miller, R.G.; Weiner, M.W. Gray matter perfusion correlates with disease severity in ALS. Neurology, 2010, 74(10), 821-827.
169. Sospedra, M.; Martin, R. Immunology of multiple sclerosis. Annu. Rev. Immunol., 2005, 23, 683-747.
170. Fugger, L.; Friese, M.A.; Bell, J.I. From genes to function: the next challenge to understanding multiple sclerosis. Nat. Rev. Immunol., 2009, 9(6), 408-417.
171. Lopez-Diego, R.S.; Weiner, H.L. Novel therapeutic strategies for multiple sclerosis--a multifaceted adversary. Nat. Rev. Drug Discov., 2008, 7(11), 909-925.
172. Kotter, M.R.; Stadelmann, C.; Hartung, H.P. Enhancing remyelination in disease--can we wrap it up? Brain, 2011, 134(Pt 7), 1882-1900.
173. Arnett, H.A.; Mason, J.; Marino, M.; Suzuki, K.; Matsushima, G.K.; Ting, J.P. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat. Neurosci., 2001, 4(11), 1116-1122.
174. Foote, A.K.; Blakemore, W.F. Inflammation stimulates remyelination in areas of chronic demyelination. Brain, 2005, 128(Pt 3), 528-539.
175. Nikic, I.; Merkler, D.; Sorbara, C.; Brinkoetter, M.; Kreutzfeldt, M.; Bareyre, F.M.; Bruck, W.; Bishop, D.; Misgeld, T.; Kerschensteiner, M. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat. Med., 2011, 17(4), 495-499.