Innate Immunity in the CNS: Redefining the relationship between the CNS and its Environment

Neuron

Volumn 78, Issue 2, 2013, Pages 214-232

  Lampron, Antoine ^a   ElAli, Ayman ^a   Rivest, Serge ^a  

^a LAVAL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BETA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 14; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 6; LYMPHOTOXIN; SCLEROPROTEIN; TOLL LIKE RECEPTOR 11; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 9; TRANSFORMING GROWTH FACTOR BETA;

ALZHEIMER DISEASE; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN INFECTION; BRAIN INJURY; CENTRAL NERVOUS SYSTEM; CYTOKINE PRODUCTION; ENDOTHELIUM CELL; ENVIRONMENTAL IMPACT; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOPATHOLOGY; INNATE IMMUNITY; MICROGLIA; MULTIPLE SCLEROSIS; NEUROPATHOLOGY; PATTERN RECOGNITION; PERICYTE; PHAGOCYTOSIS; PRIORITY JOURNAL; REVIEW; VIRUS ENTRY;

ANIMALS; BLOOD-BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; CYTOKINES; ENVIRONMENT; HUMANS; IMMUNITY, INNATE; MODELS, IMMUNOLOGICAL; NEUROGLIA;

EID: 84876784407     PISSN: 08966273     EISSN: 10974199     Source Type: Journal    
DOI: 10.1016/j.neuron.2013.04.005     Document Type: Review

References (204)

1. Abbott N.J., Rönnbäck L., Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 2006, 7:41-53.
2. Abraham M., Shapiro S., Karni A., Weiner H.L., Miller A. Gelatinases (MMP-2 and MMP-9) are preferentially expressed by Th1 vs. Th2 cells. J. Neuroimmunol. 2005, 163:157-164.
3. Agrawal S.M., Yong V.W. The many faces of EMMPRIN - roles in neuroinflammation. Biochim. Biophys. Acta 2011, 1812:213-219.
4. Agrawal S., Anderson P., Durbeej M., van Rooijen N., Ivars F., Opdenakker G., Sorokin L.M. Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J. Exp. Med. 2006, 203:1007-1019.
5. Agrawal S.M., Silva C., Tourtellotte W.W., Yong V.W. EMMPRIN: a novel regulator of leukocyte transmigration into the CNS in multiple sclerosis and experimental autoimmune encephalomyelitis. J. Neurosci. 2011, 31:669-677.
6. Ajami B., Bennett J.L., Krieger C., Tetzlaff W., Rossi F.M. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 2007, 10:1538-1543.
7. Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G.M., Cooper N.R., Eikelenboom P., Emmerling M., Fiebich B.L., et al. Inflammation and Alzheimer's disease. Neurobiol. Aging 2000, 21:383-421.
8. Al Ahmad A., Taboada C.B., Gassmann M., Ogunshola O.O. Astrocytes and pericytes differentially modulate blood-brain barrier characteristics during development and hypoxic insult. J. Cereb. Blood Flow Metab. 2011, 31:693-705.
9. Alvarez J.I., Dodelet-Devillers A., Kebir H., Ifergan I., Fabre P.J., Terouz S., Sabbagh M., Wosik K., Bourbonnière L., Bernard M., et al. The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science 2011, 334:1727-1731.
10. Amiry-Moghaddam M., Ottersen O.P. The molecular basis of water transport in the brain. Nat. Rev. Neurosci. 2003, 4:991-1001.
11. Andersson A., Covacu R., Sunnemark D., Danilov A.I., Dal Bianco A., Khademi M., Wallström E., Lobell A., Brundin L., Lassmann H., Harris R.A. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J. Leukoc. Biol. 2008, 84:1248-1255.
12. András I.E., Pu H., Tian J., Deli M.A., Nath A., Hennig B., Toborek M. Signaling mechanisms of HIV-1 Tat-induced alterations of claudin-5 expression in brain endothelial cells. J. Cereb. Blood Flow Metab. 2005, 25:1159-1170.
13. Argaw A.T., Zhang Y., Snyder B.J., Zhao M.L., Kopp N., Lee S.C., Raine C.S., Brosnan C.F., John G.R. IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program. J. Immunol. 2006, 177:5574-5584.
14. Armulik A., Genové G., Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell 2011, 21:193-215.
15. Azevedo F.A., Carvalho L.R., Grinberg L.T., Farfel J.M., Ferretti R.E., Leite R.E., Jacob Filho W., Lent R., Herculano-Houzel S. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J. Comp. Neurol. 2009, 513:532-541.
16. Balabanov R., Washington R., Wagnerova J., Dore-Duffy P. CNS microvascular pericytes express macrophage-like function, cell surface integrin alpha M, and macrophage marker ED-2. Microvasc. Res. 1996, 52:127-142.
17. Balistreri C.R., Grimaldi M.P., Chiappelli M., Licastro F., Castiglia L., Listì F., Vasto S., Lio D., Caruso C., Candore G. Association between the polymorphisms of TLR4 and CD14 genes and Alzheimer's disease. Curr. Pharm. Des. 2008, 14:2672-2677.
18. Banchereau J., Pascual V., O'Garra A. From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat. Immunol. 2012, 13:925-931.
19. Banks W.A., Broadwell R.D. Blood to brain and brain to blood passage of native horseradish peroxidase, wheat germ agglutinin, and albumin: pharmacokinetic and morphological assessments. J. Neurochem. 1994, 62:2404-2419.
20. Banks W.A., Kastin A.J., Akerstrom V. HIV-1 protein gp120 crosses the blood-brain barrier: role of adsorptive endocytosis. Life Sci. 1997, 61:PL119-PL125.
21. Banks W.A., Owen J.B., Erickson M.A. Insulin in the brain: there and back again. Pharmacol. Ther. 2012, 136:82-93.
22. Bechmann I., Priller J., Kovac A., Böntert M., Wehner T., Klett F.F., Bohsung J., Stuschke M., Dirnagl U., Nitsch R. Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages. Eur. J. Neurosci. 2001, 14:1651-1658.
23. Beck K., Schachtrup C. Vascular damage in the central nervous system: a multifaceted role for vascular-derived TGF-β. Cell Tissue Res. 2012, 347:187-201.
24. 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, 68:409-427.
25. Bell R.D., Winkler E.A., Singh I., Sagare A.P., Deane R., Wu Z., Holtzman D.M., Betsholtz C., Armulik A., Sallstrom J., et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 2012, 485:512-516.
26. Bellavance M.A., Rivest S. The neuroendocrine control of the innate immune system in health and brain diseases. Immunol. Rev. 2012, 248:36-55.
27. Bencurova E., Mlynarcik P., Bhide M. An insight into the ligand-receptor interactions involved in the translocation of pathogens across blood-brain barrier. FEMS Immunol. Med. Microbiol. 2011, 63:297-318.
28. Bettens K., Sleegers K., Van Broeckhoven C. Genetic insights in Alzheimer's disease. Lancet Neurol. 2013, 12:92-104.
29. Boche D., Perry V.H., Nicoll J.A. Review: activation patterns ofmicroglia and their identification in the human brain. Neuropathol. Appl. Neurobiol. 2013, 39:3-18.
30. Boissonneault V., Filali M., Lessard M., Relton J., Wong G., Rivest S. Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer's disease. Brain 2009, 132:1078-1092.
31. Bozoyan L., Khlghatyan J., Saghatelyan A. Astrocytes control the development of the migration-promoting vasculature scaffold in the postnatal brain via VEGF signaling. J. Neurosci. 2012, 32:1687-1704.
32. Brown J., Wang H., Hajishengallis G.N., Martin M. TLR-signaling networks: an integration of adaptor molecules, kinases, and cross-talk. J. Dent. Res. 2011, 90:417-427.
33. Burt R.K., Loh Y., Cohen B., Stefoski D., Balabanov R., Katsamakis G., Oyama Y., Russell E.J., Stern J., Muraro P., et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009, 8:244-253.
34. 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, 23:297-308.
35. Butt A.M., Kalsi A. Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions. J. Cell. Mol. Med. 2006, 10:33-44.
36. Cagnin A., Brooks D.J., Kennedy A.M., Gunn R.N., Myers R., Turkheimer F.E., Jones T., Banati R.B. In-vivo measurement of activated microglia in dementia. Lancet 2001, 358:461-467.
37. Carson M.J., Doose J.M., Melchior B., Schmid C.D., Ploix C.C. CNS immune privilege: hiding in plain sight. Immunol. Rev. 2006, 213:48-65.
38. Cartier N., Hacein-Bey-Abina S., Bartholomae C.C., Veres G., Schmidt M., Kutschera I., Vidaud M., Abel U., Dal-Cortivo L., Caccavelli L., et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 2009, 326:818-823.
39. Chauhan V.S., Furr S.R., Sterka D.G., Nelson D.A., Moerdyk-Schauwecker M., Marriott I., Grdzelishvili V.Z. Vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses. Virology 2010, 400:187-196.
40. Chen Y.C., Yip P.K., Huang Y.L., Sun Y., Wen L.L., Chu Y.M., Chen T.F. Sequence variants of toll like receptor 4 and late-onset Alzheimer's disease. PLoS ONE 2012, 7:e50771.
41. Chung I.Y., Benveniste E.N. Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta. J. Immunol. 1990, 144:2999-3007.
42. Cirrito J.R., Deane R., Fagan A.M., Spinner M.L., Parsadanian M., Finn M.B., Jiang H., Prior J.L., Sagare A., Bales K.R., et al. P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J. Clin. Invest. 2005, 115:3285-3290.
43. Coisne C., Lyck R., Engelhardt B. Live cell imaging techniques to study Tcell trafficking across the blood-brain barrier invitro and invivo. Fluids Barriers CNS 2013, 10:7.
44. Compston A., Coles A. Multiple sclerosis. Lancet 2008, 372:1502-1517.
45. Conductier G., Blondeau N., Guyon A., Nahon J.L., Rovère C. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J. Neuroimmunol. 2010, 224:93-100.
46. Constantin D., Cordenier A., Robinson K., Ala'Aldeen D.A., Murphy S. Neisseria meningitidis-induced death of cerebrovascular endothelium: mechanisms triggering transcriptional activation of inducible nitric oxide synthase. J. Neurochem. 2004, 89:1166-1174.
47. Coureuil M., Mikaty G., Miller F., Lécuyer H., Bernard C., Bourdoulous S., Duménil G., Mège R.M., Weksler B.B., Romero I.A., et al. Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science 2009, 325:83-87.
48. Coureuil M., Lécuyer H., Scott M.G., Boularan C., Enslen H., Soyer M., Mikaty G., Bourdoulous S., Nassif X., Marullo S. Meningococcus Hijacks a β2-adrenoceptor/β-Arrestin pathway to cross brain microvasculature endothelium. Cell 2010, 143:1149-1160.
49. Coyne C.B., Kim K.S., Bergelson J.M. Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2. EMBO J. 2007, 26:4016-4028.
50. Creagh E.M., O'Neill L.A. TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol. 2006, 27:352-357.
51. Cristante E., McArthur S., Mauro C., Maggioli E., Romero I.A., Wylezinska-Arridge M., Couraud P.O., Lopez-Tremoleda J., Christian H.C., Weksler B.B., et al. Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications. Proc. Natl. Acad. Sci. USA 2013, 110:832-841.
52. Daffis S., Samuel M.A., Suthar M.S., Keller B.C., Gale M., Diamond M.S. Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection. J. Virol. 2008, 82:8465-8475.
53. Daneman R., Zhou L., Kebede A.A., Barres B.A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010, 468:562-566.
54. Danese S., Dejana E., Fiocchi C. Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J. Immunol. 2007, 178:6017-6022.
55. Davalos D., Ryu J.K., Merlini M., Baeten K.M., Le Moan N., Petersen M.A., Deerinck T.J., Smirnoff D.S., Bedard C., Hakozaki H., et al. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun 2012, 3:1227.
56. Deane R., Du Yan S., Submamaryan R.K., LaRue B., Jovanovic S., Hogg E., Welch D., Manness L., Lin C., Yu J., et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat. Med. 2003, 9:907-913.
57. Deane R., Wu Z., Sagare A., Davis J., Du Yan S., Hamm K., Xu F., Parisi M., LaRue B., Hu H.W., et al. LRP/amyloid β-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 2004, 43:333-344.
58. Deane R., Sagare A., Zlokovic B.V. The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. Curr. Pharm. Des. 2008, 14:1601-1605.
59. Deane R., Singh I., Sagare A.P., Bell R.D., Ross N.T., LaRue B., Love R., Perry S., Paquette N., Deane R.J., et al. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Invest. 2012, 122:1377-1392.
60. DeKosky S.T., Styren S.D., O'Malley M.E., Goss J.R., Kochanek P., Marion D., Evans C.H., Robbins P.D. Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat brain. Ann. Neurol. 1996, 39:123-127.
61. del Zoppo G.J., Milner R. Integrin-matrix interactions in the cerebral microvasculature. Arterioscler. Thromb. Vasc. Biol. 2006, 26:1966-1975.
62. Dello Russo C., Polak P.E., Mercado P.R., Spagnolo A., Sharp A., Murphy P., Kamal A., Burrows F.J., Fritz L.C., Feinstein D.L. The heat-shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitis. J. Neurochem. 2006, 99:1351-1362.
63. Dinarello C.A. Immunological and inflammatory functions of the interleukin-1 family. Annu. Rev. Immunol. 2009, 27:519-550.
64. Dore-Duffy P., Washington R., Dragovic L. Expression of endothelial cell activation antigens in microvessels from patients with multiple sclerosis. Adv. Exp. Med. Biol. 1993, 331:243-248.
65. Duchini A., Govindarajan S., Santucci M., Zampi G., Hofman F.M. Effects of tumor necrosis factor-alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells. J. Investig. Med. 1996, 44:474-482.
66. Edelman D.A., Jiang Y., Tyburski J.G., Wilson R.F., Steffes C.P. Lipopolysaccharide activation of pericyte's Toll-like receptor-4 regulates co-culture permeability. Am. J. Surg. 2007, 193:730-735.
67. ElAli A., Hermann D.M. Apolipoprotein E controls ATP-binding cassette transporters in the ischemic brain. Sci. Signal. 2010, 3:ra72.
68. ElAli A., Hermann D.M. ATP-binding cassette transporters and their roles in protecting the brain. Neuroscientist 2011, 17:423-436.
69. Etienne-Manneville S., Manneville J.B., Adamson P., Wilbourn B., Greenwood J., Couraud P.O. ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. J. Immunol. 2000, 165:3375-3383.
70. Farina C., Aloisi F., Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol. 2007, 28:138-145.
71. Farkas E., Luiten P.G. Cerebral microvascular pathology in aging and Alzheimer's disease. Prog. Neurobiol. 2001, 64:575-611.
72. Fernandes K.S., Brum D.G., Palei A.C., Sandrim V.C., Guerreiro C.T., Tanus-Santos J.E., Barreira A.A. Functional MMP-9 polymorphisms modulate plasma MMP-9 levels in multiple sclerosis patients. J. Neuroimmunol. 2012, 249:56-59.
73. Fernández-Klett F., Offenhauser N., Dirnagl U., Priller J., Lindauer U. Pericytes in capillaries are contractile invivo, but arterioles mediate functional hyperemia in the mouse brain. Proc. Natl. Acad. Sci. USA 2010, 107:22290-22295.
74. Fiala M., Lin J., Ringman J., Kermani-Arab V., Tsao G., Patel A., Lossinsky A.S., Graves M.C., Gustavson A., Sayre J., et al. Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients. J. Alzheimers Dis. 2005, 7:221-232. discussion 255-262.
75. Floris S., Blezer E.L., Schreibelt G., Döpp E., van der Pol S.M., Schadee-Eestermans I.L., Nicolay K., Dijkstra C.D., de Vries H.E. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study. Brain 2004, 127:616-627.
76. Friedlander R.M., Gagliardini V., Hara H., Fink K.B., Li W., MacDonald G., Fishman M.C., Greenberg A.H., Moskowitz M.A., Yuan J. Expression of a dominant negative mutant of interleukin-1 beta converting enzyme in transgenic mice prevents neuronal cell death induced by trophic factor withdrawal and ischemic brain injury. J. Exp. Med. 1997, 185:933-940.
77. Friedman A., Kaufer D., Heinemann U. Blood-brain barrier breakdown-inducing astrocytic transformation: novel targets for the prevention of epilepsy. Epilepsy Res. 2009, 85:142-149.
78. Furr S.R., Chauhan V.S., Sterka D., Grdzelishvili V., Marriott I. Characterization of retinoic acid-inducible gene-I expression in primary murine glia following exposure to vesicular stomatitis virus. J. Neurovirol. 2008, 14:503-513.
79. García-Amado M., Prensa L. Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex. PLoS ONE 2012, 7:e38692.
80. Gehrmann J., Matsumoto Y., Kreutzberg G.W. Microglia: intrinsic immuneffector cell of the brain. Brain Res. Brain Res. Rev. 1995, 20:269-287.
81. Ginhoux F., Greter M., Leboeuf M., Nandi S., See P., Gokhan S., Mehler M.F., Conway S.J., Ng L.G., Stanley E.R., et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010, 330:841-845.
82. Gloor S.M., Wachtel M., Bolliger M.F., Ishihara H., Landmann R., Frei K. Molecular and cellular permeability control at the blood-brain barrier. Brain Res. Brain Res. Rev. 2001, 36:258-264.
83. Gosselin D., Rivest S. Immune mechanisms underlying the beneficial effects of autologous hematopoietic stem cell transplantation in multiple sclerosis. Neurotherapeutics 2011, 8:643-649.
84. Graeber M.B., Streit W.J., Kiefer R., Schoen S.W., Kreutzberg G.W. New expression of myelomonocytic antigens by microglia and perivascular cells following lethal motor neuron injury. J. Neuroimmunol. 1990, 27:121-132.
85. Hanamsagar R., Hanke M.L., Kielian T. Toll-like receptor (TLR) and inflammasome actions in the central nervous system. Trends Immunol. 2012, 33:333-342.
86. Hanke M.L., Kielian T. Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin. Sci. 2011, 121:367-387.
87. Hawkins B.T., Davis T.P. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev. 2005, 57:173-185.
88. Hellström M., Gerhardt H., Kalén M., Li X., Eriksson U., Wolburg H., Betsholtz C. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol. 2001, 153:543-553.
89. Hermann D.M., Elali A. The abluminal endothelial membrane in neurovascular remodeling in health and disease. Sci. Signal. 2012, 5:re4.
90. Herx L.M., Rivest S., Yong V.W. Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 beta is required for the production of ciliary neurotrophic factor. J. Immunol. 2000, 165:2232-2239.
91. Hickey W.F., Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen invivo. Science 1988, 239:290-292.
92. Holtzman D.M., Herz J., Bu G. Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med 2012, 2:a006312.
93. Honig S.M., Fu S., Mao X., Yopp A., Gunn M.D., Randolph G.J., Bromberg J.S. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent Tcell chemotaxis to lymph nodes. J. Clin. Invest. 2003, 111:627-637.
94. Hume D.A., MacDonald K.P. Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood 2012, 119:1810-1820.
95. Ifergan I., Kébir H., Bernard M., Wosik K., Dodelet-Devillers A., Cayrol R., Arbour N., Prat A. The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain 2008, 131:785-799.
96. Igarashi Y., Utsumi H., Chiba H., Yamada-Sasamori Y., Tobioka H., Kamimura Y., Furuuchi K., Kokai Y., Nakagawa T., Mori M., Sawada N. Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood-brain barrier. Biochem. Biophys. Res. Commun. 1999, 261:108-112.
97. Imbimbo B.P. An update on the efficacy of non-steroidal anti-inflammatory drugs in Alzheimer's disease. Expert Opin. Investig. Drugs 2009, 18:1147-1168.
98. Jacobs S., Doering L.C. Astrocytes prevent abnormal neuronal development in the fragile x mouse. J. Neurosci. 2010, 30:4508-4514.
99. Jaerve A., Müller H.W. Chemokines in CNS injury and repair. Cell Tissue Res. 2012, 349:229-248.
100. John G.R., Lee S.C., Song X., Rivieccio M., Brosnan C.F. IL-1-regulated responses in astrocytes: relevance to injury and recovery. Glia 2005, 49:161-176.
101. Kaminska B., Kocyk M., Kijewska M. TGF beta signaling and its role in glioma pathogenesis. Adv. Exp. Med. Biol. 2013, 986:171-187.
102. Kanmogne G.D., Primeaux C., Grammas P. HIV-1 gp120 proteins alter tight junction protein expression and brain endothelial cell permeability: implications for the pathogenesis of HIV-associated dementia. J. Neuropathol. Exp. Neurol. 2005, 64:498-505.
103. Klein I., Cornejo J.C., Polakos N.K., John B., Wuensch S.A., Topham D.J., Pierce R.H., Crispe I.N. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood 2007, 110:4077-4085.
104. Koehler R.C., Roman R.J., Harder D.R. Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 2009, 32:160-169.
105. Kooij G., Mizee M.R., van Horssen J., Reijerkerk A., Witte M.E., Drexhage J.A., van der Pol S.M., van Het Hof B., Scheffer G., Scheper R., et al. Adenosine triphosphate-binding cassette transporters mediate chemokine (C-C motif) ligand 2 secretion from reactive astrocytes: relevance to multiple sclerosis pathogenesis. Brain 2011, 134:555-570.
106. Kovac A., Erickson M.A., Banks W.A. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide. J. Neuroinflammation 2011, 8:139.
107. Kumar H., Kawai T., Akira S. Pathogen recognition by the innate immune system. Int. Rev. Immunol. 2011, 30:16-34.
108. Laflamme N., Lacroix S., Rivest S. An essential role of interleukin-1beta in mediating NF-kappaB activity and COX-2 transcription in cells of the blood-brain barrier in response to a systemic and localized inflammation but not during endotoxemia. J. Neurosci. 1999, 19:10923-10930.
109. Lampron A., Gosselin D., Rivest S. Targeting the hematopoietic system for the treatment of Alzheimer's disease. Brain Behav. Immun. 2011, 25(Suppl 1):S71-S79.
110. Lampron A., Lessard M., Rivest S. Effects of myeloablation, peripheral chimerism, and whole-body irradiation on the entry of bone marrow-derived cells into the brain. Cell Transplant. 2012, 21:1149-1159.
111. Larochelle C., Alvarez J.I., Prat A. How do immune cells overcome the blood-brain barrier in multiple sclerosis?. FEBS Lett. 2011, 585:3770-3780.
112. Lech M., Avila-Ferrufino A., Skuginna V., Susanti H.E., Anders H.J. Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome-related mRNAs in humans and mice. Int. Immunol. 2010, 22:717-728.
113. Leppert D., Ford J., Stabler G., Grygar C., Lienert C., Huber S., Miller K.M., Hauser S.L., Kappos L. Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain 1998, 121:2327-2334.
114. Ley K., Laudanna C., Cybulsky M.I., Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat. Rev. Immunol. 2007, 7:678-689.
115. Lindberg R.L., De Groot C.J., Montagne L., Freitag P., van der Valk P., Kappos L., Leppert D. The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain 2001, 124:1743-1753.
116. Mackic J.B., Bading J., Ghiso J., Walker L., Wisniewski T., Frangione B., Zlokovic B.V. Circulating amyloid-beta peptide crosses the blood-brain barrier in aged monkeys and contributes to Alzheimer's disease lesions. Vascul. Pharmacol. 2002, 38:303-313.
117. Mahley R.W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988, 240:622-630.
118. Maimone D., Gregory S., Arnason B.G., Reder A.T. Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis. J. Neuroimmunol. 1991, 32:67-74.
119. Majumdar A., Cruz D., Asamoah N., Buxbaum A., Sohar I., Lobel P., Maxfield F.R. Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils. Mol. Biol. Cell 2007, 18:1490-1496.
120. Malm T., Koistinaho M., Muona A., Magga J., Koistinaho J. The role and therapeutic potential of monocytic cells in Alzheimer's disease. Glia 2010, 58:889-900.
121. Maroso M., Balosso S., Ravizza T., Liu J., Aronica E., Iyer A.M., Rossetti C., Molteni M., Casalgrandi M., Manfredi A.A., et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat. Med. 2010, 16:413-419.
122. Marta M., Meier U.C., Lobell A. Regulation of autoimmune encephalomyelitis by toll-like receptors. Autoimmun. Rev. 2009, 8:506-509.
123. Martinez F.O., Sica A., Mantovani A., Locati M. Macrophage activation and polarization. Front. Biosci. 2008, 13:453-461.
124. Mason J.L., Suzuki K., Chaplin D.D., Matsushima G.K. Interleukin-1beta promotes repair of the CNS. J. Neurosci. 2001, 21:7046-7052.
125. McGeer P.L., Schulzer M., McGeer E.G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology 1996, 47:425-432.
126. Michaud J.P., Richard K.L., Rivest S. MyD88-adaptor protein acts as a preventive mechanism for memory deficits in a mouse model of Alzheimer's disease. Mol. Neurodegener. 2011, 6:5.
127. Michaud J.P., Hallé M., Lampron A., Thériault P., Préfontaine P., Filali M., Tribout-Jover P., Lanteigne A.M., Jodoin R., Cluff C., et al. Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer's disease-related pathology. Proc. Natl. Acad. Sci. USA 2013, 110:1941-1946.
128. Minagar A., Alexander J.S. Blood-brain barrier disruption in multiple sclerosis. Mult. Scler. 2003, 9:540-549.
129. Minoretti P., Gazzaruso C., Vito C.D., Emanuele E., Bianchi M., Coen E., Reino M., Geroldi D. Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer's disease. Neurosci. Lett. 2006, 391:147-149.
130. Montgomery S.L., Mastrangelo M.A., Habib D., Narrow W.C., Knowlden S.A., Wright T.W., Bowers W.J. Ablation of TNF-RI/RII expression in Alzheimer's disease mice leads to an unexpected enhancement of pathology: implications for chronic pan-TNF-α suppressive therapeutic strategies in the brain. Am. J. Pathol. 2011, 179:2053-2070.
131. Moraes C.F., Lins T.C., Carmargos E.F., Naves J.O., Pereira R.W., Nóbrega O.T. Lessons from genome-wide association studies findings in Alzheimer's disease. Psychogeriatrics 2012, 12:62-73.
132. Moses A.V., Bloom F.E., Pauza C.D., Nelson J.A. Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism. Proc. Natl. Acad. Sci. USA 1993, 90:10474-10478.
133. Muldoon L.L., Alvarez J.I., Begley D.J., Boado R.J., Del Zoppo G.J., Doolittle N.D., Engelhardt B., Hallenbeck J.M., Lonser R.R., Ohlfest J.R., et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J. Cereb. Blood Flow Metab. 2013, 33:13-21.
134. Murawski M.R., McGinnes L.W., Finberg R.W., Kurt-Jones E.A., Massare M.J., Smith G., Heaton P.M., Fraire A.E., Morrison T.G. Newcastle disease virus-like particles containing respiratory syncytial virus G protein induced protection in BALB/c mice, with no evidence of immunopathology. J. Virol. 2010, 84:1110-1123.
135. Naert G., Rivest S. CC chemokine receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease. J. Neurosci. 2011, 31:6208-6220.
136. Naert G., Rivest S. Age-related changes in synaptic markers and monocyte subsets link the cognitive decline of APP(Swe)/PS1 mice. Front Cell Neurosci 2012, 6:51.
137. Nagyoszi P., Wilhelm I., Farkas A.E., Fazakas C., Dung N.T., Haskó J., Krizbai I.A. Expression and regulation of toll-like receptors in cerebral endothelial cells. Neurochem. Int. 2010, 57:556-564.
138. Nakamuta S., Endo H., Higashi Y., Kousaka A., Yamada H., Yano M., Kido H. Human immunodeficiency virus type 1 gp120-mediated disruption of tight junction proteins by induction of proteasome-mediated degradation of zonula occludens-1 and -2 in human brain microvascular endothelial cells. J. Neurovirol. 2008, 14:186-195.
139. Napoli I., Neumann H. Protective effects of microglia in multiple sclerosis. Exp. Neurol. 2010, 225:24-28.
140. Olson J.K., Miller S.D. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J. Immunol. 2004, 173:3916-3924.
141. Pachter J.S., de Vries H.E., Fabry Z. The blood-brain barrier and its role in immune privilege in the central nervous system. J. Neuropathol. Exp. Neurol. 2003, 62:593-604.
142. Pardridge W.M. Blood-brain barrier drug targeting: the future of brain drug development. Mol. Interv. 2003, 3:90-105. 51.
143. Peltier D.C., Simms A., Farmer J.R., Miller D.J. Human neuronal cells possess functional cytoplasmic and TLR-mediated innate immune pathways influenced by phosphatidylinositol-3 kinase signaling. J. Immunol. 2010, 184:7010-7021.
144. Pepe M.G., Curtiss L.K. Apolipoprotein E is a biologically active constituent of the normal immunoregulatory lipoprotein, LDL-In. J. Immunol. 1986, 136:3716-3723.
145. Polman C.H., Uitdehaag B.M. New and emerging treatment options for multiple sclerosis. Lancet Neurol. 2003, 2:563-566.
146. Prat A., Biernacki K., Lavoie J.F., Poirier J., Duquette P., Antel J.P. Migration of multiple sclerosis lymphocytes through brain endothelium. Arch. Neurol. 2002, 59:391-397.
147. Raggers R.J., Vogels I., van Meer G. Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor. Biochem. J. 2001, 357:859-865.
148. Rao U.S., Fine R.L., Scarborough G.A. Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem. Pharmacol. 1994, 48:287-292.
149. Ray S., Britschgi M., Herbert C., Takeda-Uchimura Y., Boxer A., Blennow K., Friedman L.F., Galasko D.R., Jutel M., Karydas A., et al. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat. Med. 2007, 13:1359-1362.
150. Reed-Geaghan E.G., Savage J.C., Hise A.G., Landreth G.E. CD14 and toll-like receptors 2 and 4 are required for fibrillar Abeta-stimulated microglial activation. J. Neurosci. 2009, 29:11982-11992.
151. Ribes S., Adam N., Schütze S., Regen T., Redlich S., Janova H., Borisch A., Hanisch U.K., Nau R. The nucleotide-binding oligomerization domain-containing-2 ligand muramyl dipeptide enhances phagocytosis and intracellular killing of Escherichia coli K1 by Toll-like receptor agonists in microglial cells. J. Neuroimmunol. 2012, 252:16-23.
152. Richard K.L., Filali M., Préfontaine P., Rivest S. Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid beta 1-42 and delay the cognitive decline in a mouse model of Alzheimer's disease. J. Neurosci. 2008, 28:5784-5793.
153. Ritter M.R., Banin E., Moreno S.K., Aguilar E., Dorrell M.I., Friedlander M. Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy. J. Clin. Invest. 2006, 116:3266-3276.
154. Rivest S. Regulation of innate immune responses in the brain. Nat. Rev. Immunol. 2009, 9:429-439.
155. Rosenzweig H.L., Planck S.R., Rosenbaum J.T. NLRs in immune privileged sites. Curr. Opin. Pharmacol. 2011, 11:423-428.
156. Rubio-Perez J.M., Morillas-Ruiz J.M. A review: inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal 2012, 2012:756357.
157. Rucker H.K., Wynder H.J., Thomas W.E. Cellular mechanisms of CNS pericytes. Brain Res. Bull. 2000, 51:363-369.
158. Sagar D., Lamontagne A., Foss C.A., Khan Z.K., Pomper M.G., Jain P. Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood-brain barrier through paracellular transmigration and ERK activation. J. Neuroinflammation 2012, 9:245.
159. Schilling M., Strecker J.K., Schäbitz W.R., Ringelstein E.B., Kiefer R. Effects of monocyte chemoattractant protein 1 on blood-borne cell recruitment after transient focal cerebral ischemia in mice. Neuroscience 2009, 161:806-812.
160. Schiltz J.C., Sawchenko P.E. Distinct brain vascular cell types manifest inducible cyclooxygenase expression as a function of the strength and nature of immune insults. J. Neurosci. 2002, 22:5606-5618.
161. Schulze C., Firth J.A. Immunohistochemical localization of adherens junction components in blood-brain barrier microvessels of the rat. J. Cell Sci. 1993, 104:773-782.
162. Shechter R., Schwartz M. Harnessing monocyte-derived macrophages to control central nervous system pathologies: no longer 'if' but 'how'. J. Pathol. 2013, 229:332-346.
163. Simard A.R., Rivest S. Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia. FASEB J. 2004, 18:998-1000.
164. Simard A.R., Soulet D., Gowing G., Julien J.P., Rivest S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 2006, 49:489-502.
165. Skripuletz T., Hackstette D., Bauer K., Gudi V., Pul R., Voss E., Berger K., Kipp M., Baumgärtner W., Stangel M. Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain 2013, 136:147-167.
166. Smith D.E., Lipsky B.P., Russell C., Ketchem R.R., Kirchner J., Hensley K., Huang Y., Friedman W.J., Boissonneault V., Plante M.M., et al. A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1. Immunity 2009, 30:817-831.
167. Song M., Jin J., Lim J.E., Kou J., Pattanayak A., Rehman J.A., Kim H.D., Tahara K., Lalonde R., Fukuchi K. TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease. J. Neuroinflammation 2011, 8:92.
168. Soulet D., Rivest S. Bone-marrow-derived microglia: myth or reality?. Curr. Opin. Pharmacol. 2008, 8:508-518.
169. Soulet D., Rivest S. Microglia. Curr. Biol. 2008, 18:R506-R508.
170. Spörri B., Bickel M., Dobbelaere D., Machado J., Lottaz D. Soluble interleukin-1 receptor-reverse signaling in innate immunoregulation. Cytokine Growth Factor Rev. 2001, 12:27-32.
171. Srinivasan D., Yen J.H., Joseph D.J., Friedman W. Cell type-specific interleukin-1beta signaling in the CNS. J. Neurosci. 2004, 24:6482-6488.
172. Stanimirovic D., Shapiro A., Wong J., Hutchison J., Durkin J. The induction of ICAM-1 in human cerebromicrovascular endothelial cells (HCEC) by ischemia-like conditions promotes enhanced neutrophil/HCEC adhesion. J. Neuroimmunol. 1997, 76:193-205.
173. Steinman L. Inflammatory cytokines at the summits of pathological signal cascades in brain diseases. Sci. Signal. 2013, 6:pe3.
174. Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A., Rayner K.J., Boyer L., Zhong R., Frazier W.A., et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 2010, 11:155-161.
175. Strober W., Watanabe T. NOD2, an intracellular innate immune sensor involved in host defense and Crohn's disease. Mucosal Immunol. 2011, 4:484-495.
176. Tahara K., Kim H.D., Jin J.J., Maxwell J.A., Li L., Fukuchi K. Role of toll-like receptor signalling in Abeta uptake and clearance. Brain 2006, 129:3006-3019.
177. Takeichi M. Morphogenetic roles of classic cadherins. Curr. Opin. Cell Biol. 1995, 7:619-627.
178. Takeshita Y., Ransohoff R.M. Inflammatory cell trafficking across the blood-brain barrier: chemokine regulation and invitro models. Immunol. Rev. 2012, 248:228-239.
179. Terkeltaub R.A., Dyer C.A., Martin J., Curtiss L.K. Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to stimulate neutrophils. Characterization of intraarticular apo E and demonstration of apo E binding to urate crystals invivo. J. Clin. Invest. 1991, 87:20-26.
180. Town T., Laouar Y., Pittenger C., Mori T., Szekely C.A., Tan J., Duman R.S., Flavell R.A. Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat. Med. 2008, 14:681-687.
181. Uchihara T., Akiyama H., Kondo H., Ikeda K. Activated microglial cells are colocalized with perivascular deposits of amyloid-beta protein in Alzheimer's disease brain. Stroke 1997, 28:1948-1950.
182. Udan M.L., Ajit D., Crouse N.R., Nichols M.R. Toll-like receptors 2 and 4 mediate Abeta(1-42) activation of the innate immune response in a human monocytic cell line. J. Neurochem. 2008, 104:524-533.
183. Vaknin I., Kunis G., Miller O., Butovsky O., Bukshpan S., Beers D.R., Henkel J.S., Yoles E., Appel S.H., Schwartz M. Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis. PLoS ONE 2011, 6:e26921.
184. van Assema D.M., Lubberink M., Bauer M., van der Flier W.M., Schuit R.C., Windhorst A.D., Comans E.F., Hoetjes N.J., Tolboom N., Langer O., et al. Blood-brain barrier P-glycoprotein function in Alzheimer's disease. Brain 2012, 135:181-189.
185. Van Dam A.M., De Vries H.E., Kuiper J., Zijlstra F.J., De Boer A.G., Tilders F.J., Berkenbosch F. Interleukin-1 receptors on rat brain endothelial cells: a role in neuroimmune interaction?. FASEB J. 1996, 10:351-356.
186. van Vliet E.A., da Costa Araújo S., Redeker S., van Schaik R., Aronica E., Gorter J.A. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain 2007, 130:521-534.
187. Vezzani A. Inflammation and epilepsy. Epilepsy Curr. 2005, 5:1-6.
188. von Büdingen H.C., Kuo T.C., Sirota M., van Belle C.J., Apeltsin L., Glanville J., Cree B.A., Gourraud P.A., Schwartzburg A., Huerta G., et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J. Clin. Invest. 2012, 122:4533-4543.
189. Wang L.Z., Yu J.T., Miao D., Wu Z.C., Zong Y., Wen C.Q., Tan L. Genetic association of TLR4/11367 polymorphism with late-onset Alzheimer's disease in a Han Chinese population. Brain Res. 2011, 1381:202-207.
190. Weiss J.M., Downie S.A., Lyman W.D., Berman J.W. Astrocyte-derived monocyte-chemoattractant protein-1 directs the transmigration of leukocytes across a model of the human blood-brain barrier. J. Immunol. 1998, 161:6896-6903.
191. Westin K., Buchhave P., Nielsen H., Minthon L., Janciauskiene S., Hansson O. CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease. PLoS ONE 2012, 7:e30525.
192. Wiendl H., Hohlfeld R. Multiple sclerosis therapeutics: unexpected outcomes clouding undisputed successes. Neurology 2009, 72:1008-1015.
193. Wilson E.H., Weninger W., Hunter C.A. Trafficking of immune cells in the central nervous system. J. Clin. Invest. 2010, 120:1368-1379.
194. Winkler E.A., Bell R.D., Zlokovic B.V. Central nervous system pericytes in health and disease. Nat. Neurosci. 2011, 14:1398-1405.
195. Xiong H., Callaghan D., Jones A., Bai J., Rasquinha I., Smith C., Pei K., Walker D., Lue L.F., Stanimirovic D., Zhang W. ABCG2 is upregulated in Alzheimer's brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for Abeta(1-40) peptides. J. Neurosci. 2009, 29:5463-5475.
196. Yemisci M., Gursoy-Ozdemir Y., Vural A., Can A., Topalkara K., Dalkara T. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat. Med. 2009, 15:1031-1037.
197. Yoneyama M., Fujita T. Recognition of viral nucleic acids in innate immunity. Rev. Med. Virol. 2010, 20:4-22.
198. Yu J.T., Miao D., Cui W.Z., Ou J.R., Tian Y., Wu Z.C., Zhang W., Tan L. Common variants in toll-like receptor 4 confer susceptibility to Alzheimer's disease in a Han Chinese population. Curr. Alzheimer Res. 2012, 9:458-466.
199. Zambetti L.P., Laudisi F., Licandro G., Ricciardi-Castagnoli P., Mortellaro A. The rhapsody of NLRPs: master players of inflammation... and a lot more. Immunol. Res. 2012, 53:78-90.
200. Zhang W., Wang L.Z., Yu J.T., Chi Z.F., Tan L. Increased expressions of TLR2 and TLR4 on peripheral blood mononuclear cells from patients with Alzheimer's disease. J. Neurol. Sci. 2012, 315:67-71.
201. Zheng W., Monnot A.D. Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases. Pharmacol. Ther. 2012, 133:177-188.
202. Zlokovic B.V. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008, 57:178-201.
203. Zlokovic B.V. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat. Rev. Neurosci. 2011, 12:723-738.
204. Zloković B.V., Lipovac M.N., Begley D.J., Davson H., Rakić L. Transport of leucine-enkephalin across the blood-brain barrier in the perfused guinea pig brain. J. Neurochem. 1987, 49:310-315.