title: Microbial induction of vascular pathology in the CNS.
abstract: The central nervous system (CNS) is a finely tuned organ that participates in nearly every aspect of our day-to-day function. Neurons lie at the core of this functional unit and maintain an active dialogue with one another as well as their fellow CNS residents (e.g. astrocytes, oligodendrocytes, microglia). Because of this complex dialogue, it is essential that the CNS milieu be tightly regulated in order to permit uninterrupted and efficient neural chemistry. This is accomplished in part by anatomical barriers that segregate vascular components from the cerebral spinal fluid (CSF) and brain parenchyma. These barriers impede entry of noxious materials and enable the CNS to maintain requisite protein and ionic balances for constant electrochemical signaling. Under homeostatic conditions, the CNS is protected by the presence of specialized endothelium/epithelium, the blood brain barrier (BBB), and the blood-CSF barrier. However, following CNS infection these protective barriers can be comprised, sometimes resulting in severe neurological complications triggered by an imbalance or blockage of neural chemistry. In some instances, these disruptions are severe enough to be fatal. This review focuses on a selection of microbes (both viruses and parasites) that compromise vascular barriers and induce neurological complications upon gaining access to the CNS. Emphasis is placed on CNS diseases that result from a pathogenic interplay between host immune defenses and the invading microbe.
authors.affiliation: National Institute of Neurological Disorders and Stroke, The National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Kang
authors.forename: Dorian B
authors.initials: DB
authors.lastname: McGavern
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000469:parasitology / Q000473:pathology* / Q000821:virology; D018188:Cardiovirus Infections / Q000473:pathology / Q000821:virology; D002494:Central Nervous System Infections / Q000276:immunology / Q000473:pathology*; D006482:Hemorrhagic Fevers, Viral / Q000473:pathology / Q000821:virology; D006801:Humans; D008216:Lymphocytic Choriomeningitis / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus; D016779:Malaria, Cerebral / Q000469:parasitology / Q000473:pathology; D017945:Theilovirus
references.citation: Development. 1999 May;126(10):2093-102
references.pmid: 10207135
references.citation: Int Rev Neurobiol. 2007;79:73-97
references.pmid: 17531838
references.citation: J Cell Sci. 1997 Sep;110 ( Pt 17):2065-77
references.pmid: 9378757
references.citation: J Cell Biol. 1996 Apr;133(1):43-7
references.pmid: 8601611
references.citation: Nat Med. 2009 Sep;15(9):1031-7
references.pmid: 19718040
references.citation: J Virol. 2007 Dec;81(24):13469-77
references.pmid: 17928350
references.citation: J Immunol. 2003 Mar 15;170(6):2797-801
references.pmid: 12626527
references.citation: Eur J Immunol. 2000 Jul;30(7):1797-806
references.pmid: 10940868
references.citation: J Cell Biol. 2001 Aug 6;154(3):491-7
references.pmid: 11489913
references.citation: Lab Invest. 1981 Nov;45(5):435-41
references.pmid: 7029133
references.citation: Trends Immunol. 2009 Nov;30(11):522-30
references.pmid: 19775938
references.citation: Acta Neuropathol. 1983;61(3-4):183-95
references.pmid: 6606284
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 Dec;291(6):L1232-45
references.pmid: 16891393
references.citation: Cell. 1978 Jun;14(2):423-8
references.pmid: 667949
references.citation: Vascul Pharmacol. 2002 Jun;38(6):323-37
references.pmid: 12529927
references.citation: J Pathol Bacteriol. 1961 Jul;82:13-7
references.pmid: 13700345
references.citation: J Infect Dis. 1999 Feb;179 Suppl 1:S199-202
references.pmid: 9988185
references.citation: J Biol Chem. 2006 Nov 24;281(47):35593-7
references.pmid: 17005550
references.citation: J Exp Med. 2000 Oct 16;192(8):1205-11
references.pmid: 11034611
references.citation: Neurobiol Dis. 2010 Jan;37(1):13-25
references.pmid: 19664713
references.citation: Nat Immunol. 2007 Nov;8(11):1159-64
references.pmid: 17952040
references.citation: Blood Coagul Fibrinolysis. 2000 Jul;11(5):461-83
references.pmid: 10937808
references.citation: Infect Immun. 2006 Jan;74(1):645-53
references.pmid: 16369021
references.citation: J Cell Physiol. 2007 Oct;213(1):221-8
references.pmid: 17476691
references.citation: J Immunol. 2006 Jan 15;176(2):1180-4
references.pmid: 16394007
references.citation: EMBO Rep. 2008 Aug;9(8):742-7
references.pmid: 18600233
references.citation: J Virol. 2006 Jun;80(11):5168-78
references.pmid: 16698997
references.citation: Nat Immunol. 2002 Feb;3(2):151-8
references.pmid: 11812992
references.citation: J Exp Med. 2000 Jun 5;191(11):1829-39
references.pmid: 10839800
references.citation: J Biol Chem. 2006 Mar 31;281(13):8379-88
references.pmid: 16439355
references.citation: Nat Rev Immunol. 2005 Sep;5(9):722-35
references.pmid: 16138104
references.citation: Am J Pathol. 1996 Nov;149(5):1745-62
references.pmid: 8909263
references.citation: J Virol. 2006 Feb;80(3):1222-30
references.pmid: 16414999
references.citation: Infect Immun. 2005 Apr;73(4):2288-97
references.pmid: 15784573
references.citation: Nat Med. 2009 May;15(5):519-27
references.pmid: 19396173
references.citation: J Virol. 2005 Aug;79(16):10442-50
references.pmid: 16051836
references.citation: Mol Biol Cell. 2000 Dec;11(12):4131-42
references.pmid: 11102513
references.citation: J Neuroimmunol. 1995 Oct;62(1):35-42
references.pmid: 7499490
references.citation: Nat Med. 2001 Oct;7(10):1123-7
references.pmid: 11590435
references.citation: J Biol Chem. 2003 Dec 5;278(49):49644-51
references.pmid: 14512431
references.citation: Acta Neuropathol. 1984;63(3):229-39
references.pmid: 6464679
references.citation: J Infect Dis. 1999 Feb;179 Suppl 1:S1-7
references.pmid: 9988155
references.citation: Curr Neuropharmacol. 2008 Sep;6(3):179-92
references.pmid: 19506719
references.citation: J Cell Biol. 2001 May 28;153(5):933-46
references.pmid: 11381080
references.citation: Proc Natl Acad Sci U S A. 1989 Jul;86(14):5572-4
references.pmid: 2501793
references.citation: J Virol. 2004 Mar;78(6):2943-7
references.pmid: 14990712
references.citation: Int J Parasitol. 2006 May 1;36(5):541-6
references.pmid: 16600245
references.citation: PLoS Pathog. 2007 Sep 7;3(9):1271-80
references.pmid: 17907801
references.citation: J Virol. 2002 Mar;76(5):2518-28
references.pmid: 11836430
references.citation: Lab Invest. 2002 Sep;82(9):1155-66
references.pmid: 12218076
references.citation: J Virol. 1987 May;61(5):1507-16
references.pmid: 3033278
references.citation: Blood. 2007 Oct 1;110(7):2545-55
references.pmid: 17625065
references.citation: Parasitology. 1993 Aug;107 ( Pt 2):125-34
references.pmid: 8414666
references.citation: J Neuropathol Exp Neurol. 1977 Jan;36(1):21-40
references.pmid: 188995
references.citation: Blood. 2006 Jun 15;107(12):4754-62
references.pmid: 16514057
references.citation: Curr Mol Med. 2009 Mar;9(2):174-85
references.pmid: 19275625
references.citation: J Immunol. 2003 Feb 15;170(4):2221-8
references.pmid: 12574396
references.citation: Virology. 2001 May 25;284(1):20-5
references.pmid: 11352664
references.citation: J Gen Virol. 1980 Jan;46(1):169-77
references.pmid: 6243340
references.citation: J Immunol. 1995 May 15;154(10):5293-301
references.pmid: 7537304
references.citation: J Immunol. 1996 Mar 1;156(5):1886-96
references.pmid: 8596041
references.citation: Scand J Immunol. 1986 Aug;24(2):153-62
references.pmid: 3489282
references.citation: J Virol. 2004 Oct;78(19):10370-7
references.pmid: 15367603
references.citation: Trends Immunol. 2009 Nov;30(11):547-56
references.pmid: 19783480
references.citation: J Neurosci Res. 1996 Aug 15;45(4):364-74
references.pmid: 8872896
references.citation: Virology. 1990 May;176(1):244-54
references.pmid: 2158691
references.citation: Nat Med. 2009 Aug;15(8):914-20
references.pmid: 19633658
references.citation: J Exp Med. 1989 Jun 1;169(6):1977-91
references.pmid: 2499653
references.citation: J Infect Dis. 2003 Feb 1;187(3):461-6
references.pmid: 12552430
references.citation: Parasite Immunol. 2008 Oct;30(10):544-53
references.pmid: 18665903
references.citation: Microvasc Res. 2001 Jan;61(1):130-43
references.pmid: 11162203
references.citation: Trends Immunol. 2003 Sep;24(9):491-9
references.pmid: 12967673
references.citation: J Cereb Blood Flow Metab. 2006 Jun;26(6):797-810
references.pmid: 16192992
references.citation: J Infect Dis. 1999 Feb;179 Suppl 1:S188-91
references.pmid: 9988183
references.citation: Am J Pathol. 1981 Feb;102(2):146-50
references.pmid: 7468764
references.citation: J Cell Biol. 1998 Apr 6;141(1):199-208
references.pmid: 9531559
references.citation: Lancet. 2008 May 10;371(9624):1612-23
references.pmid: 18468545
references.citation: Nature. 2009 Jan 8;457(7226):191-5
references.pmid: 19011611
references.citation: Virology. 2007 Jul 20;364(1):45-54
references.pmid: 17391724
references.citation: J Exp Med. 2002 May 20;195(10):1371-7
references.pmid: 12021316
references.citation: J Cell Biol. 1994 Dec;127(6 Pt 1):1617-26
references.pmid: 7798316
references.citation: Nat Med. 2008 Dec;14(12):1377-83
references.pmid: 19029985
references.citation: J Virol. 1997 Oct;71(10):7832-40
references.pmid: 9311871
references.citation: Int Immunol. 2003 May;15(5):633-40
references.pmid: 12697663
references.citation: PLoS One. 2008 Aug 22;3(8):e3037
references.pmid: 18725947
references.citation: J Biol Chem. 2004 Dec 31;279(53):55602-8
references.pmid: 15485832
references.citation: J Virol. 2009 Apr;83(7):3069-77
references.pmid: 19153231
references.citation: Infect Immun. 1989 Apr;57(4):1218-26
references.pmid: 2925247
references.citation: Semin Immunopathol. 2009 Nov;31(4):497-511
references.pmid: 19779720
references.citation: Cell Immunol. 1978 Mar 1;36(1):143-50
references.pmid: 305287
references.citation: Viral Immunol. 2004;17(3):390-400
references.pmid: 15357905
references.citation: J Exp Med. 2006 Apr 17;203(4):1007-19
references.pmid: 16585265
references.citation: J Exp Med. 2008 Apr 14;205(4):811-23
references.pmid: 18347102
references.citation: Neuroscience. 1998 Oct;86(4):1245-57
references.pmid: 9697130
references.citation: Acta Neuropathol. 2003 Jun;105(6):586-92
references.pmid: 12734665
references.citation: J Cell Biol. 1996 Oct;135(2):497-510
references.pmid: 8896605
references.citation: J Exp Med. 1991 Dec 1;174(6):1425-9
references.pmid: 1683893
references.citation: PLoS Pathog. 2009 Apr;5(4):e1000369
references.pmid: 19343215
references.citation: Nat Med. 1999 Apr;5(4):423-6
references.pmid: 10202932
references.citation: J Cell Sci. 2000 Jul;113 ( Pt 13):2363-74
references.pmid: 10852816
references.citation: Virology. 2003 Jan 5;305(1):1-9
references.pmid: 12504535
references.citation: Eur J Immunol. 2008 Apr;38(4):1082-95
references.pmid: 18383042
references.citation: J Cereb Blood Flow Metab. 2005 May;25(5):593-606
references.pmid: 15689955
references.citation: J Cell Sci. 1994 Dec;107 ( Pt 12):3655-63
references.pmid: 7706414
references.citation: Q J Exp Physiol Cogn Med Sci. 1960 Oct;45:343-8
references.pmid: 13766495
references.citation: Nat Cell Biol. 2008 Aug;10(8):923-34
references.pmid: 18604199
references.citation: Thromb Haemost. 2005 Aug;94(2):254-61
references.pmid: 16113813
references.citation: J Biol Chem. 2009 Jul 10;284(28):19053-66
references.pmid: 19423710
references.citation: Transplant Rev. 1974;19(0):89-120
references.pmid: 4601807
references.citation: Exp Physiol. 2007 Jul;92(4):641-6
references.pmid: 17483201
references.citation: Blood. 2002 Oct 1;100(7):2479-86
references.pmid: 12239159
references.citation: J Neuroinflammation. 2008 Jul 07;5:31
references.pmid: 18606015
references.citation: Infect Immun. 2001 Apr;69(4):2364-71
references.pmid: 11254594
references.citation: Clin Microbiol Rev. 2004 Jan;17(1):174-207
references.pmid: 14726460
references.citation: J Infect Dis. 2008 Apr 1;197(7):1062-73
references.pmid: 18419473
references.citation: Br J Exp Pathol. 1955 Jun;36(3):268-82
references.pmid: 13239983
references.citation: J Virol. 2001 Nov;75(22):11025-33
references.pmid: 11602743
references.citation: J Immunol. 1999 Jul 15;163(2):553-7
references.pmid: 10395639
references.citation: J Virol. 2006 Oct;80(20):10109-16
references.pmid: 17005688
references.citation: Nat Rev Immunol. 2004 Mar;4(3):169-80
references.pmid: 15039754
references.citation: J Infect Dis. 2007 Nov 15;196 Suppl 2:S337-46
references.pmid: 17940969
references.citation: Nat Immunol. 2002 Oct;3(10):918-25
references.pmid: 12352968
references.citation: J Gen Virol. 2000 Sep;81(Pt 9):2155-2159
references.pmid: 10950971
references.citation: J Cell Biol. 1998 Apr 20;141(2):397-408
references.pmid: 9548718
references.citation: J Infect Dis. 2003 Apr 15;187(8):1283-90
references.pmid: 12696008
references.citation: J Immunol. 2007 May 1;178(9):5779-88
references.pmid: 17442962
references.citation: J Physiol. 1972 Apr;222(2):447-74
references.pmid: 4624453
references.citation: J Immunol. 2002 Dec 1;169(11):6369-75
references.pmid: 12444144
references.citation: J Virol. 1988 Oct;62(10):3589-96
references.pmid: 2843661
references.citation: Cell Immunol. 1987 Jun;107(1):8-14
references.pmid: 3495350
references.citation: Nat Rev Immunol. 2003 Aug;3(8):677-85
references.pmid: 12974482
references.citation: J Exp Med. 2006 Aug 7;203(8):1963-75
references.pmid: 16847068
references.citation: Ann N Y Acad Sci. 2003 Dec;1010:582-6
references.pmid: 15033796
references.citation: Nature. 1986 May 15-21;321(6067):239-43
references.pmid: 3086743
references.citation: J Neuroimmunol. 2001 Aug 30;118(2):256-67
references.pmid: 11498260
references.citation: J Cell Biol. 1999 Oct 4;147(1):185-94
references.pmid: 10508865
references.citation: Nat Rev Immunol. 2007 Jul;7(7):556-67
references.pmid: 17589545
references.citation: Redox Rep. 1999;4(6):333-5
references.pmid: 10772080
references.citation: J Immunol. 1982 Nov;129(5):2213-8
references.pmid: 6749988
references.citation: Int J Biochem Cell Biol. 2006 Feb;38(2):222-33
references.pmid: 16257565
references.citation: J Biol Chem. 2002 Jul 26;277(30):27501-9
references.pmid: 12021270
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1081-8
references.pmid: 15886398
references.citation: Mol Biochem Parasitol. 2001 Jul;115(2):129-43
references.pmid: 11420100
references.citation: J Clin Invest. 2004 Mar;113(6):885-94
references.pmid: 15067321
references.citation: Mol Membr Biol. 2002 Apr-Jun;19(2):103-12
references.pmid: 12126228
references.citation: Am J Pathol. 1986 Apr;123(1):16-24
references.pmid: 2421578
references.citation: Nat Neurosci. 2007 Nov;10(11):1369-76
references.pmid: 17965657
references.citation: Front Biosci. 2008 May 01;13:4529-43
references.pmid: 18508527
references.citation: J Immunol. 2005 Jun 1;174(11):6854-62
references.pmid: 15905527
references.citation: J Exp Med. 1993 Jan 1;177(1):145-53
references.pmid: 8418196
references.citation: Virology. 2003 Jan 5;305(1):115-23
references.pmid: 12504546
references.citation: FASEB J. 2009 Oct;23(10):3449-58
references.pmid: 19535685
references.citation: J Virol. 1986 Dec;60(3):1163-5
references.pmid: 3023668
references.citation: J Virol. 2006 Jul;80(14):7235-44
references.pmid: 16809329
references.citation: J Gen Virol. 2010 Feb;91(Pt 2):352-61
references.pmid: 19828757
references.citation: Cell Host Microbe. 2008 Aug 14;4(2):179-87
references.pmid: 18692777
references.citation: Am J Pathol. 2003 Dec;163(6):2371-82
references.pmid: 14633609
references.citation: Trends Immunol. 2007 Jan;28(1):5-11
references.pmid: 17140851
references.citation: Cell. 2005 Dec 2;123(5):889-901
references.pmid: 16325582
references.citation: J Neuropathol Exp Neurol. 1977 Jan;36(1):9-20
references.pmid: 833620
references.citation: FEBS J. 2007 Sep;274(18):4670-9
references.pmid: 17824953
references.citation: J Pathol. 2000 Feb;190(3):343-8
references.pmid: 10685068
references.citation: J Cell Biol. 2003 May 12;161(3):459-60
references.pmid: 12743096
references.citation: Brain Res Brain Res Rev. 2005 Dec 1;50(1):7-13
references.pmid: 16291072
references.citation: Eur J Immunol. 2000 Jun;30(6):1646-55
references.pmid: 10898501
references.citation: Clin Exp Immunol. 2000 Apr;120(1):125-33
references.pmid: 10759773
references.citation: Fed Proc. 1971 Nov-Dec;30(6):1831-41
references.pmid: 4942053
references.citation: Nature. 2009 Jan 8;457(7226):155-6
references.pmid: 19129836
references.citation: J Cell Biol. 1967 Jul;34(1):207-17
references.pmid: 6033532
references.citation: Neuropathol Appl Neurobiol. 1988 Jan-Feb;14(1):1-17
references.pmid: 3374751
references.citation: J Immunol. 2000 Sep 15;165(6):3375-83
references.pmid: 10975856
references.citation: J Cell Biol. 1999 Dec 13;147(6):1351-63
references.pmid: 10601346
references.citation: J Neuroimmunol. 1998 Jun 15;86(2):202-12
references.pmid: 9663567
references.citation: Cell. 1999 Jul 23;98(2):147-57
references.pmid: 10428027
references.citation: Hamostaseologie. 2008 Feb;28(1-2):77-84
references.pmid: 18278167
references.citation: Annu Rev Microbiol. 2005;59:279-98
references.pmid: 16153171
references.citation: Physiol Rev. 2007 Jan;87(1):315-424
references.pmid: 17237348
references.citation: J Physiol. 1990 Oct;429:47-62
references.pmid: 2277354
references.citation: J Med Virol. 2003 Jun;70(2):273-5
references.pmid: 12696116
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Nov;293(5):L1219-29
references.pmid: 17766589
references.citation: Eur J Immunol. 1997 Jul;27(7):1719-25
references.pmid: 9247583
references.citation: J Immunol. 1996 Mar 1;156(5):1897-1907
references.pmid: 8596042
references.citation: J Infect Dis. 2007 Nov 15;196 Suppl 2:S296-304
references.pmid: 17940964
references.citation: J Infect Dis. 2003 Dec 1;188(11):1630-8
references.pmid: 14639532
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3243-8
references.pmid: 17360632
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4814-9
references.pmid: 18347328
references.citation: J Cell Biol. 2003 May 12;161(3):653-60
references.pmid: 12743111
references.citation: Immunol Res. 2005;31(1):1-12
references.pmid: 15591618
references.citation: J Immunol. 2008 Jan 15;180(2):1217-30
references.pmid: 18178862
references.citation: Am J Trop Med Hyg. 1994 Nov;51(5):642-7
references.pmid: 7985757
references.citation: Epilepsia. 2007 Apr;48(4):732-42
references.pmid: 17319915
references.citation: J Cell Biol. 1993 Dec;123(6 Pt 2):1777-88
references.pmid: 8276896
references.citation: J Virol. 2010 Jan;84(1):312-20
references.pmid: 19828618
references.citation: J Virol. 1996 Apr;70(4):2208-14
references.pmid: 8642644
references.citation: Prog Biophys Mol Biol. 2003 Jan;81(1):1-44
references.pmid: 12475568
references.citation: Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):729-35
references.pmid: 15681301
references.citation: Histochem Cell Biol. 2008 Jul;130(1):55-70
references.pmid: 18415116
references.citation: J Exp Med. 1991 Oct 1;174(4):785-90
references.pmid: 1680957
references.citation: J Immunol. 1994 Feb 1;152(3):1237-45
references.pmid: 7507962
references.citation: J Anat. 1990 Jun;170:111-23
references.pmid: 2254158
references.citation: J Infect. 2000 Jan;40(1):16-20
references.pmid: 10762106
references.citation: J Cell Sci. 2003 Nov 15;116(Pt 22):4615-28
references.pmid: 14576355
references.citation: Blood. 2000 Jul 15;96(2):719-26
references.pmid: 10887140
references.citation: Science. 1998 Feb 13;279(5353):1034-7
references.pmid: 9461435
references.citation: Scand J Immunol. 1995 Jul;42(1):110-8
references.pmid: 7543210
references.citation: J Biol Chem. 2002 Jan 4;277(1):455-61
references.pmid: 11689568