Thinking about HIV: The intersection of virus, neuroinflammation and cognitive dysfunction

Immunologic Research

Volumn 48, Issue 1-3, 2010, Pages 40-58

  Grovit Ferbas, K ^a,b   Harris White, M E ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Brain tumor; CNS IRIS; Dementia; HIV; Microbial translocation; Neuropathogenesis

Indexed keywords

AMYLOID BETA PROTEIN; CARBON TETRACHLORIDE; CD11B ANTIGEN; CD14 ANTIGEN; CD16 ANTIGEN; CD3 ANTIGEN; CD4 ANTIGEN; CD45 ANTIGEN; CELL SURFACE PROTEIN; CHEMOKINE RECEPTOR CCR3; CHEMOKINE RECEPTOR CCR5; ENDOTOXIN; FRACTALKINE; GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 41; INTERLEUKIN 1; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; NEF PROTEIN; RANTES; T LYMPHOCYTE RECEPTOR; TAU PROTEIN; TRANSACTIVATOR PROTEIN; TRANSFORMING GROWTH FACTOR BETA ACTIVATED KINASE 1; TRANSFORMING GROWTH FACTOR BETA2; UNINDEXED DRUG; VIRUS RNA;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ALZHEIMER DISEASE; AUTISM; BLOOD BRAIN BARRIER; CD4 LYMPHOCYTE COUNT; CENTRAL NERVOUS SYSTEM INFECTION; CEREBRAL PALSY; CHILD; COGNITIVE DEFECT; DEMENTIA; DEVELOPMENTAL DISORDER; EPSTEIN BARR VIRUS INFECTION; GENE TRANSLOCATION; GLIOBLASTOMA; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME; IMMUNOSURVEILLANCE; LEUKOENCEPHALOPATHY; MACROPHAGE; MICROGLIA; MOTOR DYSFUNCTION; NERVE CELL PLASTICITY; NERVE DEGENERATION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PERIPHERAL NEUROPATHY; PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; PRIMATE; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; SPINAL CORD DISEASE;

AIDS DEMENTIA COMPLEX; ANIMALS; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; BRAIN; HIV; HUMANS; IMMUNOLOGIC SURVEILLANCE; MACROPHAGES; MICROGLIA; NEURITIS; NEUROPROTECTIVE AGENTS; VIRAL LOAD; VIRUS REPLICATION;

EID: 78549265452     PISSN: 0257277X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s12026-010-8166-x     Document Type: Review

References (201)

1. WHO/UNAIDS. Report on the global AIDS epidemic; 2009.
2. M Kaul J Zheng S Okamoto HE Gendelman SA Lipton 2005 HIV-1 infection and AIDS: consequences for the central nervous system Cell Death Differ 12 Suppl 1 878 892 15832177 15832177
3. KC Williams S Corey SV Westmoreland D Pauley H Knight C deBakker X Alvarez AA Lackner 2001 Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS J Exp Med 193 8 905 915 11304551
4. SJ Bissel CA Wiley 2004 Human immunodeficiency virus infection of the brain: pitfalls in evaluating infected/affected cell populations Brain Pathol 14 1 97 108 14997942
5. T Fischer-Smith C Bell S Croul M Lewis J Rappaport 2008 Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies J Neurovirol 14 4 318 326 18780233
6. MA Cosenza ML Zhao Q Si SC Lee 2002 Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis Brain Pathol 12 4 442 455 12408230
7. Y Yi C Lee QH Liu BD Freedman RG Collman 2004 Chemokine receptor utilization and macrophage signaling by human immunodeficiency virus type 1 gp120: implications for neuropathogenesis J Neurovirol 10 Suppl 1 91 96 14982745 14982745
8. L Agrawal JP Louboutin E Marusich BA Reyes EJ Van Bockstaele DS Strayer 2010 Dopaminergic neurotoxicity of HIV-1 gp120: reactive oxygen species as signaling intermediates Brain Res 1306 116 130 19815008 Epub@2009 Oct 6.:116-30
9. SF An M Groves B Giometto AA Beckett F Scaravilli 1999 Detection and localisation of HIV-1 DNA and RNA in fixed adult AIDS brain by polymerase chain reaction/in situ hybridisation technique Acta Neuropathol 98 5 481 487 10541871
10. SF An M Groves F Gray F Scaravilli 1999 Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals J Neuropathol Exp Neurol 58 11 1156 1162 10560658
11. LE Davis BL Hjelle VE Miller, et al. 1992 Early viral brain invasion in iatrogenic human immunodeficiency virus infection Neurology 42 9 1736 1739 1513462
12. A Borjabad AI Brooks DJ Volsky 2010 Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders J Neuroimmune Pharmacol 5 1 44 62 19697136
13. NS Ivey AG MacLean AA Lackner 2009 Acquired immunodeficiency syndrome and the blood-brain barrier J Neurovirol 15 2 111 122 19306229
14. R Dunfee ER Thomas PR Gorry J Wang P Ancuta D Gabuzda 2006 Mechanisms of HIV-1 neurotropism Curr HIV Res 4 3 267 278 16842080
15. H Adle-Biassette Y Levy M Colombel F Poron S Natchev C Keohane F Gray 1995 Neuronal apoptosis in HIV infection in adults Neuropathol Appl Neurobiol 21 3 218 227 7477730
16. F Gray H dle-Biassette F Brion T Ereau MI le V Levy G Corcket 2000 Neuronal apoptosis in human immunodeficiency virus infection J Neurovirol 6 Suppl 1 S38 S43 10871764
17. F Gray H dle-Biassette F Chretien GG de la Lorin G Force C Keohane 2001 Neuropathology and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments Clin Neuropathol 20 4 146 155 11495003
18. L Agrawal JP Louboutin BA Reyes EJ Van Bockstaele DS Strayer 2006 Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis Gene Ther 13 23 1645 1656 16871233
19. JP Louboutin BA Reyes L Agrawal CR Maxwell EJ Van Bockstaele DS Strayer 2010 Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120-protection by gene delivery of antioxidant enzymes Neurobiol Dis 38 2 313 325 20219678
20. JP Louboutin BA Reyes L Agrawal EJ Van Bockstaele DS Strayer 2010 HIV-1 gp120-induced neuroinflammation: relationship to neuron loss and protection by rSV40-delivered antioxidant enzymes Exp Neurol 221 1 231 245 19913017
21. JP Louboutin BA Reyes L Agrawal BE Van DS Strayer 2007 Strategies for CNS-directed gene delivery: in vivo gene transfer to the brain using SV40-derived vectors Gene Ther 14 12 939 949 17443215
22. A Chaudhuri B Yang HE Gendelman Y Persidsky GD Kanmogne 2008 STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier Blood 111 4 2062 2072 18003888
23. GD Kanmogne K Schall J Leibhart B Knipe HE Gendelman Y Persidsky 2007 HIV-1 gp120 compromises blood-brain barrier integrity and enhances monocyte migration across blood-brain barrier: implication for viral neuropathogenesis J Cereb Blood Flow Metab 27 1 123 134 16685256
24. M Mukhtar RJ Pomerantz 2000 Development of an in vitro blood-brain barrier model to study molecular neuropathogenesis and neurovirologic disorders induced by human immunodeficiency virus type 1 infection J Hum Virol 3 6 324 334 11100913
25. Y Persidsky J Zheng D Miller HE Gendelman 2000 Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia J Leukoc Biol 68 3 413 422 10985259
26. PR Harrington G Schnell SL Letendre, et al. 2009 Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course AIDS 23 8 907 915 19414991
27. SK Pillai SL Pond Y Liu, et al. 2006 Genetic attributes of cerebrospinal fluid-derived HIV-1 env Brain 129 Pt 7 1872 1883 16735456
28. MC Strain S Letendre SK Pillai, et al. 2005 Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy J Virol 79 3 1772 1788 15650202
29. K Ritola CD Pilcher SA Fiscus, et al. 2004 Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type 1 J Virol 78 20 11208 11218 15452240
30. K Ritola K Robertson SA Fiscus C Hall R Swanstrom 2005 Increased human immunodeficiency virus type 1 (HIV-1) env compartmentalization in the presence of HIV-1-associated dementia J Virol 79 16 10830 10834 16051875
31. K Robertson S Fiscus C Kapoor, et al. 1998 CSF, plasma viral load and HIV associated dementia J Neurovirol 4 1 90 94 9531015
32. BJ Brew L Pemberton P Cunningham MG Law 1997 Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage J Infect Dis 175 4 963 966 9086160
33. A Scourfield L Waters M Nelson 2010 Spectrum of neurological disease in patients with discordant HIV-1 RNA levels in plasma and cerebrospinal fluid J Infect 60 3 251 252 20035786
34. PP Christo DB Greco AW Aleixo JA Livramento 2007 Factors influencing cerebrospinal fluid, plasma HIV-1 RNA detection rate in patients with, without opportunistic neurological disease during the HAART era BMC Infect Dis 7 147 18096083
35. PP Christo MC Vilela TL Bretas RB Domingues DB Greco JA Livramento AL Teixeira 2009 Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system J Neurol Sci 287 1-2 79 83 19782379
36. G Schnell S Spudich P Harrington RW Price R Swanstrom 2009 Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia PLoS Pathog 5 4 e1000395 19390619
37. S Staprans N Marlowe D Glidden, et al. 1999 Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection AIDS 13 9 1051 1061 10397535
38. EC Caragounis M Gisslen M Lindh C Nordborg S Westergren L Hagberg B Svennerholm 2008 Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem Acta Neurol Scand 117 2 108 116 18184346
39. A Ohagen A Devitt KJ Kunstman, et al. 2003 Genetic and functional analysis of full-length human immunodeficiency virus type 1 env genes derived from brain and blood of patients with AIDS J Virol 77 22 12336 12345 14581570
40. G Schnell RW Price R Swanstrom S Spudich 2010 Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection J Virol 84 5 2395 2407 20015984
41. J Chang R Jozwiak B Wang, et al. 1998 Unique HIV type 1 V3 region sequences derived from six different regions of brain: region-specific evolution within host-determined quasispecies AIDS Res Hum Retrovir 14 1 25 30 9453248
42. SM Di F Gray T Leitner F Chiodi 1996 Analysis of ENV V3 sequences from HIV-1-infected brain indicates restrained virus expression throughout the disease J Med Virol 49 1 41 48
43. SM Di S Wilt F Gray M Dubois-Dalcq F Chiodi 1996 HIV type 1 V3 sequences and the development of dementia during AIDS AIDS Res Hum Retrovir 12 6 471 476
44. SM Di F Sabri T Leitner B Svennerholm L Hagberg G Norkrans F Chiodi 1995 Reverse transcriptase sequence of paired isolates of cerebrospinal fluid and blood from patients infected with human immunodeficiency virus type 1 during zidovudine treatment J Clin Microbiol 33 2 352 355
45. L Monno SM Di GB Zimatore, et al. 1998 Measurement of viral sequences in cerebrospinal fluid of AIDS patients with cerebral white-matter lesions using polymerase chain reaction AIDS 12 6 581 590 9583597
46. YK Donaldson JE Bell EC Holmes ES Hughes HK Brown P Simmonds 1994 In vivo distribution and cytopathology of variants of human immunodeficiency virus type 1 showing restricted sequence variability in the V3 loop J Virol 68 9 5991 6005 7545945
47. S Gartner RA McDonald EA Hunter F Bouwman Y Liu M Popovic 1997 Gp120 sequence variation in brain and in T-lymphocyte human immunodeficiency virus type 1 primary isolates J Hum Virol 1 1 3 18 10195226
48. ES Hughes JE Bell P Simmonds 1997 Investigation of the dynamics of the spread of human immunodeficiency virus to brain and other tissues by evolutionary analysis of sequences from the p17gag and env genes J Virol 71 2 1272 1280 8995651
49. BT Korber KJ Kunstman BK Patterson M Furtado MM McEvilly R Levy SM Wolinsky 1994 Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences J Virol 68 11 7467 7481 7933130
50. A Morris M Marsden K Halcrow ES Hughes RP Brettle JE Bell P Simmonds 1999 Mosaic structure of the human immunodeficiency virus type 1 genome infecting lymphoid cells and the brain: evidence for frequent in vivo recombination events in the evolution of regional populations J Virol 73 10 8720 8731 10482626
51. S Pang HV Vinters T Akashi WA O'Brien IS Chen 1991 HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease J Acquir Immune Defic Syndr 4 11 1082 1092 1684385
52. C Power JC McArthur RT Johnson DE Griffin JD Glass S Perryman B Chesebro 1994 Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences J Virol 68 7 4643 4649 8207838
53. AB van't Wout LJ Ran CL Kuiken NA Kootstra ST Pals H Schuitemaker 1998 Analysis of the temporal relationship between human immunodeficiency virus type 1 quasispecies in sequential blood samples and various organs obtained at autopsy J Virol 72 1 488 496 9420250
54. TH Wang YK Donaldson RP Brettle JE Bell P Simmonds 2001 Identification of shared populations of human immunodeficiency virus type 1 infecting microglia and tissue macrophages outside the central nervous system J Virol 75 23 11686 11699 11689650
55. JK Wong CC Ignacio F Torriani D Havlir NJ Fitch DD Richman 1997 In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues J Virol 71 3 2059 2071 9032338
56. N Sheehy U Desselberger H Whitwell JK Ball 1996 Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 during zidovudine (AZT) therapy J Gen Virol 77 Pt 5 1071 1081 8609473
57. P Shapshak DM Segal KA Crandall, et al. 1999 Independent evolution of HIV type 1 in different brain regions AIDS Res Hum Retrovir 15 9 811 820 10381169
58. TK Smit BJ Brew W Tourtellotte S Morgello BB Gelman NK Saksena 2004 Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment J Virol 78 18 10133 10148 15331746
59. TK Smit B Wang T Ng R Osborne B Brew NK Saksena 2001 Varied tropism of HIV-1 isolates derived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): evidence for neurotropic HIV variants Virology 279 2 509 526 11162807
60. PR Gorry G Bristol JA Zack, et al. 2001 Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity J Virol 75 21 10073 10089 11581376
61. KC Olivieri KA Agopian J Mukerji D Gabuzda 2010 Evidence for adaptive evolution at the divergence between lymphoid and brain HIV-1 nef genes AIDS Res Hum Retrovir 26 4 495 500 20377428
62. ER Thomas RL Dunfee J Stanton D Bogdan K Kunstman SM Wolinsky D Gabuzda 2007 High frequency of defective vpu compared with tat and rev genes in brain from patients with HIV type 1-associated dementia AIDS Res Hum Retrovir 23 4 575 580 17451348
63. ER Thomas RL Dunfee J Stanton, et al. 2007 Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion Virology 360 1 105 119 17084877
64. RL Dunfee ER Thomas J Wang K Kunstman SM Wolinsky D Gabuzda 2007 Loss of the N-linked glycosylation site at position 386 in the HIV envelope V4 region enhances macrophage tropism and is associated with dementia Virology 367 1 222 234 17599380
65. CL Kuiken J Goudsmit GF Weiller JS Armstrong S Hartman P Portegies J Dekker M Cornelissen 1995 Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex J Gen Virol 76 Pt 1 175 180 7844529
66. RT Reddy CL Achim DA Sirko S Tehranchi FG Kraus F Wong-Staal CA Wiley 1996 Sequence analysis of the V3 loop in brain and spleen of patients with HIV encephalitis AIDS Res Hum Retrovir 12 6 477 482 8679302
67. MC Zink AK Brice KM Kelly, et al. 2010 Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA J Infect Dis 202 1 161 170 20497048 20497048
68. MC Zink VA Laast KL Helke AK Brice SA Barber JE Clements JL Mankowski 2006 From mice to macaques-animal models of HIV nervous system disease Curr HIV Res 4 3 293 305 16842082
69. MC Zink JE Clements 2002 A novel simian immunodeficiency virus model that provides insight into mechanisms of human immunodeficiency virus central nervous system disease J Neurovirol 8 Suppl 2 42 48 12491150
70. MC Zink K Suryanarayana JL Mankowski, et al. 1999 High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis J Virol 73 12 10480 10488 10559366
71. AB Reeve NC Pearce K Patel KV Augustus FJ Novembre 2010 Neuropathogenic SIVsmmFGb genetic diversity and selection-induced tissue-specific compartmentalization during chronic infection and temporal evolution of viral genes in lymphoid tissues and regions of the central nervous system AIDS Res Hum Retrovir 26 6 663 679 20518690
72. KW Witwer L Gama M Li, et al. 2009 Coordinated regulation of SIV replication and immune responses in the CNS PLoS One 4 12 e8129 20019816
73. JE Clements M Li L Gama B Bullock LM Carruth JL Mankowski MC Zink 2005 The central nervous system is a viral reservoir in simian immunodeficiency virus-infected macaques on combined antiretroviral therapy: a model for human immunodeficiency virus patients on highly active antiretroviral therapy J Neurovirol 11 2 180 189 16036796
74. JE Clements T Babas JL Mankowski K Suryanarayana M Piatak Jr PM Tarwater JD Lifson MC Zink 2002 The central nervous system as a reservoir for simian immunodeficiency virus (SIV): steady-state levels of SIV DNA in brain from acute through asymptomatic infection J Infect Dis 186 7 905 913 12232830
75. KW Witwer JM Sisk L Gama JE Clements 2010 MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response J Immunol 184 5 2369 2376 20130213
76. WA O'Brien 1994 HIV-1 entry and reverse transcription in macrophages J Leukoc Biol 56 3 273 277 8083599
77. WA O'Brien SH Mao Y Cao JP Moore 1994 Macrophage-tropic and T-cell line-adapted chimeric strains of human immunodeficiency virus type 1 differ in their susceptibilities to neutralization by soluble CD4 at different temperatures J Virol 68 8 5264 5269 8035523
78. SA Barber DS Herbst BT Bullock L Gama JE Clements 2004 Innate immune responses and control of acute simian immunodeficiency virus replication in the central nervous system J Neurovirol 10 Suppl 1 15 20 14982734
79. SA Barber L Gama JM Dudaronek T Voelker PM Tarwater JE Clements 2006 Mechanism for the establishment of transcriptional HIV latency in the brain in a simian immunodeficiency virus-macaque model J Infect Dis 193 7 963 970 16518758
80. JM Dudaronek SA Barber JE Clements 2007 CUGBP1 is required for IFNbeta-mediated induction of dominant-negative CEBPbeta and suppression of SIV replication in macrophages J Immunol 179 11 7262 7269 18025168
81. SA Barber L Gama M Li, et al. 2006 Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: compartmentalized regulation of SIV J Infect Dis 194 7 931 938 16960781
82. DL Sodora JS Allan C Apetrei, et al. 2009 Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts Nat Med 15 8 861 865 19661993 19661993.
83. SR Broussard SI Staprans R White EM Whitehead MB Feinberg JS Allan 2001 Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease J Virol 75 5 2262 2275 11160730
84. J Taaffe A Chahroudi J Engram, et al. 2010 A five-year longitudinal analysis of sooty mangabeys naturally infected with simian immunodeficiency virus reveals a slow but progressive decline in CD4 + T-cell count whose magnitude is not predicted by viral load or immune activation J Virol 84 11 5476 5484 20335252
85. M Paiardini I Pandrea C Apetrei G Silvestri 2009 Lessons learned from the natural hosts of HIV-related viruses Ann Rev Med 60 485 495 19630581
86. I Pandrea G Silvestri C Apetrei 2009 AIDS in African nonhuman primate hosts of SIVs: a new paradigm of SIV infection Curr HIV Res 7 1 57 72 19149555
87. G Silvestri 2008 AIDS pathogenesis: a tale of two monkeys J Med Primatol 37 Suppl 2 6 12 19187426
88. G Silvestri 2009 Immunity in natural SIV infections J Intern Med 265 1 97 109 19093963
89. B Jacquelin V Mayau B Targat, et al. 2009 Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response J Clin Invest 119 12 3544 3555 19959873
90. MC Cumont O Diop B Vaslin, et al. 2008 Early divergence in lymphoid tissue apoptosis between pathogenic and nonpathogenic simian immunodeficiency virus infections of nonhuman primates J Virol 82 3 1175 1184 18032487
91. Y Ziv N Ron O Butovsky, et al. 2006 Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood Nat Neurosci 9 2 268 275 16415867 16415867
92. GM Lewitus H Cohen M Schwartz 2008 Reducing post-traumatic anxiety by immunization Brain Behav Immun 22 7 1108 1114 18562161 18562161
93. J Kipnis H Cohen M Cardon Y Ziv M Schwartz 2004 T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions Proc Natl Acad Sci USA 101 21 8180 8185 15141078 15141078
94. GM Lewitus A Wilf-Yarkoni Y Ziv M Shabat-Simon R Gersner A Zangen M Schwartz 2009 Vaccination as a novel approach for treating depressive behavior Biol Psychiatry 65 4 283 288 18722594 18722594
95. G Moalem R Leibowitz-Amit E Yoles F Mor IR Cohen M Schwartz 1999 Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy Nat Med 5 1 49 55 9883839 9883839
96. O Rapalino O Lazarov-Spiegler E Agranov, et al. 1998 Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats Nat Med 4 7 814 821 9662373 9662373
97. E Hauben E Agranov A Gothilf U Nevo A Cohen I Smirnov L Steinman M Schwartz 2001 Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease J Clin Invest 108 4 591 599 11518733 11518733
98. PM Thompson RA Dutton KM Hayashi AW Toga OL Lopez HJ Aizenstein JT Becker 2005 Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4 + T lymphocyte decline Proc Natl Acad Sci USA 102 43 15647 15652 16227428 16227428
99. IC Anthony SN Ramage FW Carnie P Simmonds JE Bell 2005 Influence of HAART on HIV-related CNS disease and neuroinflammation J Neuropathol Exp Neurol 64 6 529 536 15977645 15977645
100. A Eden RW Price S Spudich D Fuchs L Hagberg M Gisslen 2007 Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy J Infect Dis 196 12 1779 1783 18190258 18190258
101. R Ellis D Langford E Masliah 2007 HIV and antiretroviral therapy in the brain: neuronal injury and repair Nat Rev Neurosci 8 1 33 44 17180161 17180161
102. N Sacktor RH Lyles R Skolasky, et al. 2001 HIV-associated neurologic disease incidence changes:: Multicenter AIDS Cohort Study, 1990-1998 Neurology 56 2 257 260 11160967 11160967
103. N Sacktor PM Tarwater RL Skolasky JC McArthur OA Selnes J Becker B Cohen EN Miller 2001 CSF antiretroviral drug penetrance and the treatment of HIV-associated psychomotor slowing Neurology 57 3 542 544 11502933 11502933
104. CM Marra D Lockhart JR Zunt M Perrin RW Coombs AC Collier 2003 Changes in CSF and plasma HIV-1 RNA and cognition after starting potent antiretroviral therapy Neurology 60 8 1388 1390 12707454 12707454
105. LA Cysique P Maruff BJ Brew 2004 Antiretroviral therapy in HIV infection: are neurologically active drugs important? Arch Neurol 61 11 1699 1704 15534181 15534181
106. SA Shelburne 3rd RJ Hamill MC Rodriguez-Barradas, et al. 2002 Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy Medicine (Baltimore) 81 3 213 227 11997718
107. JA McCombe RN Auer FG Maingat S Houston MJ Gill C Power 2009 Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS: outcome and epidemiology Neurology 72 9 835 841 19255411 19255411
108. M Kaul GA Garden SA Lipton 2001 Pathways to neuronal injury and apoptosis in HIV-associated dementia Nature 410 6831 988 994 11309629 11309629
109. C Power MJ Gill RT Johnson 2002 Progress in clinical neurosciences: the neuropathogenesis of HIV infection: host-virus interaction and the impact of therapy Can J Neurol Sci 29 1 19 32 11858531 11858531
110. The neurology of AIDS, Second edn. London: Oxford University Press; 2005.
111. RJ Ellis R Deutsch RK Heaton, et al. 1997 Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group Arch Neurol 54 4 416 424 9109743 9109743
112. H Budka 1991 Neuropathology of human immunodeficiency virus infection Brain Pathol 1 3 163 175 1669705 1669705
113. DC Spencer RW Price 1992 Human immunodeficiency virus and the central nervous system Annu Rev Microbiol 46 655 693 1444270 1444270
114. JC McArthur DR Hoover H Bacellar, et al. 1993 Dementia in AIDS patients: incidence and risk factors Multicenter AIDS Cohort Study Neurology 43 11 2245 2252 8232937 8232937
115. HE Gendelman SA Lipton M Tardieu MI Bukrinsky HS Nottet 1994 The neuropathogenesis of HIV-1 infection J Leukoc Biol 56 3 389 398 8083614 8083614
116. SA Lipton HE Gendelman 1995 Seminars in medicine of the Beth Israel Hospital, Boston. Dementia associated with the acquired immunodeficiency syndrome N Engl J Med 332 14 934 940 7877652 7877652
117. JE Bell 1998 The neuropathology of adult HIV infection Rev Neurol (Paris) 154 12 816 829 9932303
118. A Nath 1999 Pathobiology of human immunodeficiency virus dementia Semin Neurol 19 2 113 127 10718533 10718533
119. JC McArthur N Haughey S Gartner K Conant C Pardo A Nath N Sacktor 2003 Human immunodeficiency virus-associated dementia: an evolving disease J Neurovirol 9 2 205 221 12707851 12707851
120. PH Cunningham DG Smith C Satchell DA Cooper B Brew 2000 Evidence for independent development of resistance to HIV-1 reverse transcriptase inhibitors in the cerebrospinal fluid AIDS 14 13 1949 1954 10997399 10997399
121. K Welch A Morse 2002 The clinical profile of end-stage AIDS in the era of highly active antiretroviral therapy AIDS Patient Care STDS 16 2 75 81 11874639 11874639
122. SA Lipton 1997 Treating AIDS dementia Science 276 5319 1629 1630 9206820 9206820
123. S Kramer-Hammerle I Rothenaigner H Wolff JE Bell R Brack-Werner 2005 Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus Virus Res 111 2 194 213 15885841 15885841
124. G Jones C Power 2006 Regulation of neural cell survival by HIV-1 infection Neurobiol Dis 21 1 1 17 16298136 16298136
125. AK Bansal CF Mactutus A Nath W Maragos KF Hauser RM Booze 2000 Neurotoxicity of HIV-1 proteins gp120 and Tat in the rat striatum Brain Res 879 1-2 42 49 11011004 11011004
126. L Agrawal JP Louboutin DS Strayer 2007 Preventing HIV-1 Tat-induced neuronal apoptosis using antioxidant enzymes: mechanistic and therapeutic implications Virology 363 2 462 472 17336361 17336361
127. MT Corasaniti MC Strongoli S Piccirilli, et al. 2000 Apoptosis induced by gp120 in the neocortex of rat involves enhanced expression of cyclooxygenase type 2 and is prevented by NMDA receptor antagonists and by the 21-aminosteroid U-74389G Biochem Biophys Res Commun 274 3 664 669 10924334
128. M Kaul SA Lipton 1999 Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis Proc Natl Acad Sci USA 96 14 8212 8216 10393974
129. O Meucci A Fatatis AA Simen TJ Bushell PW Gray RJ Miller 1998 Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity Proc Natl Acad Sci USA 95 24 14500 14505 9826729
130. B Shi GU De J He S Wang A Lorenzo J Busciglio D Gabuzda 1996 Apoptosis induced by HIV-1 infection of the central nervous system J Clin Invest 98 9 1979 1990 8903316
131. S Hu WS Sheng JR Lokensgard PK Peterson RB Rock 2009 Preferential sensitivity of human dopaminergic neurons to gp120-induced oxidative damage J Neurovirol 15 5-6 401 410 20175694
132. K Itoh P Mehraein S Weis 2000 Neuronal damage of the substantia nigra in HIV-1 infected brains Acta Neuropathol 99 4 376 384 10787036
133. DE Brenneman GL Westbrook SP Fitzgerald DL Ennist KL Elkins MR Ruff CB Pert 1988 Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide Nature 335 6191 639 642 2845276 2845276
134. J Dong H Xiong 2006 Human immunodeficiency virus type 1 gp120 inhibits long-term potentiation via chemokine receptor CXCR4 in rat hippocampal slices J Neurosci Res 83 3 489 496 16400660 16400660
135. JL Foster JV Garcia 2008 HIV-1 Nef: at the crossroads Retrovirology 5 84 18808677 18808677
136. G Trillo-Pazos E McFarlane-Abdulla IC Campbell GJ Pilkington IP Everall 2000 Recombinant nef HIV-IIIB protein is toxic to human neurons in culture Brain Res 864 2 315 326 10802040 10802040
137. G van Marle S Henry T Todoruk, et al. 2004 Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10 Virology 329 2 302 318 15518810 15518810
138. B Sporer U Koedel R Paul B Kohleisen V Erfle A Fontana HW Pfister 2000 Human immunodeficiency virus type-1 Nef protein induces blood-brain barrier disruption in the rat: role of matrix metalloproteinase-9 J Neuroimmunol 102 2 125 130 10636480 10636480
139. IC Anthony SN Ramage FW Carnie P Simmonds JE Bell 2006 Accelerated Tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy Acta Neuropathol 111 6 529 538 16718349 16718349
140. AM Fagan MA Mintun RH Mach, et al. 2006 Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans Ann Neurol 59 3 512 519 16372280 16372280
141. BJ Brew L Pemberton K Blennow A Wallin L Hagberg 2005 CSF amyloid beta42 and tau levels correlate with AIDS dementia complex Neurology 65 9 1490 1492 16275845 16275845
142. DB Clifford AM Fagan DM Holtzman JC Morris M Teshome AR Shah JS Kauwe 2009 CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease Neurology 73 23 1982 1987 19907013 19907013
143. L Pulliam 2009 HIV regulation of amyloid beta production J Neuroimmune Pharmacol 4 2 213 217 19288202 19288202
144. J Xu T Ikezu 2009 The comorbidity of HIV-associated neurocognitive disorders and Alzheimer's disease: a foreseeable medical challenge in post-HAART era J Neuroimmune Pharmacol 4 2 200 212 19016329 19016329
145. T Behnisch W Francesconi PP Sanna 2004 HIV secreted protein Tat prevents long-term potentiation in the hippocampal CA1 region Brain Res 1012 1-2 187 189 15158177 15158177
146. H Xiong YC Zeng J Zheng M Thylin HE Gendelman 1999 Soluble HIV-1 infected macrophage secretory products mediate blockade of long-term potentiation: a mechanism for cognitive dysfunction in HIV-1-associated dementia J Neurovirol 5 5 519 528 10568889 10568889
147. DM Walsh I Klyubin JV Fadeeva WK Cullen R Anwyl MS Wolfe MJ Rowan DJ Selkoe 2002 Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo Nature 416 6880 535 539 11932745 11932745
148. MY Aksenov MV Aksenova CF Mactutus RM Booze 2010 HIV-1 protein-mediated amyloidogenesis in rat hippocampal cell cultures Neurosci Lett 475 3 174 178 20363291 20363291
149. ME Harris-White T Chu Z Balverde JJ Sigel KC Flanders SA Frautschy 1998 Effects of transforming growth factor-beta (isoforms 1-3) on amyloid-beta deposition, inflammation, and cell targeting in organotypic hippocampal slice cultures J Neurosci 18 24 10366 10374 9852574 9852574
150. ME Harris-White Z Balverde GP Lim P Kim SA Miller H Hammer D Galasko SA Frautschy 2004 Role of LRP in TGFbeta2-mediated neuronal uptake of Abeta and effects on memory J Neurosci Res 77 2 217 228 15211588 15211588
151. P Eslami MF Johnson E Terzakaryan C Chew ME Harris-White 2008 TGF beta2-induced changes in LRP-1/T beta R-V and the impact on lysosomal A beta uptake and neurotoxicity Brain Res 1241 176 187 18804458 18804458
152. JR Hall SC Short 2009 Management of glioblastoma multiforme in HIV patients: a case series and review of published studies Clin Oncol (R Coll Radiol) 21 8 591 597 19589665
153. ML Rosenblum RM Levy DE Bredesen YT So W Wara JL Ziegler 1988 Primary central nervous system lymphomas in patients with AIDS Ann Neurol 23 Suppl S13 S16 2894803 2894803
154. K Welch W Finkbeiner CE Alpers W Blumenfeld RL Davis EA Smuckler JH Beckstead 1984 Autopsy findings in the acquired immune deficiency syndrome JAMA 252 9 1152 1159 6471338 6471338
155. JA Sparano K Anand J Desai RJ Mitnick GE Kalkut LH Hanau 1999 Effect of highly active antiretroviral therapy on the incidence of HIV-associated malignancies at an urban medical center J Acquir Immune Defic Syndr 21 Suppl 1 S18 S22 10430213 10430213
156. J Inungu MF Melendez JP Montgomery 2002 AIDS-related primary brain lymphoma in Michigan, January 1990 to December 2000 AIDS Patient Care STDS 16 3 107 112 11945206 11945206
157. JE Tanner C Alfieri 2001 The Epstein-Barr virus and post-transplant lymphoproliferative disease: interplay of immunosuppression, EBV, and the immune system in disease pathogenesis Transpl Infect Dis 3 2 60 69 11395971 11395971
158. O Gasser FK Bihl M Wolbers, et al. 2007 HIV patients developing primary CNS lymphoma lack EBV-specific CD4+T cell function irrespective of absolute CD4+T cell counts PLoS Med 4 3 e96 17388662 17388662
159. DT Blumenthal JJ Raizer MK Rosenblum MH Bilsky S Hariharan LE Abrey 1999 Primary intracranial neoplasms in patients with HIV Neurology 52 8 1648 1651 10331693 10331693
160. A Moulignier J Mikol G Pialoux M Eliaszewicz C Thurel JB Thiebaut 1994 Cerebral glial tumors and human immunodeficiency virus-1 infection. More than a coincidental association Cancer 74 2 686 692 8033048 8033048
161. L Tacconi S Stapleton F Signorelli DG Thomas 1996 Acquired immune deficiency syndrome (AIDS) and cerebral astrocytoma Clin Neurol Neurosurg 98 2 149 151 8836588 8836588
162. CM Koebel W Vermi JB Swann N Zerafa SJ Rodig LJ Old MJ Smyth RD Schreiber 2007 Adaptive immunity maintains occult cancer in an equilibrium state Nature 450 7171 903 907 18026089 18026089
163. M Salvati A Frati E Caroli N Russo FM Polli M Domenicucci R Delfini 2003 Glioblastoma in kidney transplant recipients. Report of five cases J Neurooncol 63 1 33 37 12814252 12814252
164. D Schiff B O'Neill E Wijdicks JH Antin PY Wen 2001 Gliomas arising in organ transplant recipients: an unrecognized complication of transplantation? Neurology 57 8 1486 1488 11673595 11673595
165. M Hajjar D Lacoste G Brossard P Morlat M Dupon LR Salmi F Dabis 1992 Non-acquired immune deficiency syndrome-defining malignancies in a hospital-based cohort of human immunodeficiency virus-infected patients: Bordeaux, France, 1985-1991. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine J Natl Cancer Inst 84 20 1593 1595 1404453 1404453
166. R Geleziunas HM Schipper MA Wainberg 1992 Pathogenesis and therapy of HIV-1 infection of the central nervous system AIDS 6 12 1411 1426 1337255 1337255
167. JP Taylor C Cupp A Diaz M Chowdhury K Khalili SA Jimenez S Amini 1992 Activation of expression of genes coding for extracellular matrix proteins in Tat-producing glioblastoma cells Proc Natl Acad Sci USA 89 20 9617 9621 1409674 1409674
168. SM Wahl JB Allen KL Hines T Imamichi AM Wahl LT Furcht JB McCarthy 1994 Synthetic fibronectin peptides suppress arthritis in rats by interrupting leukocyte adhesion and recruitment J Clin Invest 94 2 655 662 8040319 8040319
169. KW Selmaj M Farooq WT Norton CS Raine CF Brosnan 1990 Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor J Immunol 144 1 129 135 2104886 2104886
170. M Maxwell T Galanopoulos J Neville-Golden HN Antoniades 1992 Effect of the expression of transforming growth factor-beta 2 in primary human glioblastomas on immunosuppression and loss of immune surveillance J Neurosurg 76 5 799 804 1373442 1373442
171. L Emdad D Sarkar ZZ Su SG Lee DC Kang JN Bruce DJ Volsky PB Fisher 2007 Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration Pharmacol Ther 114 2 155 170 17397930 17397930
172. D Sarkar L Emdad SG Lee BK Yoo ZZ Su PB Fisher 2009 Astrocyte elevated gene-1: far more than just a gene regulated in astrocytes Cancer Res 69 22 8529 8535 19903854 19903854
173. DC Kang ZZ Su D Sarkar L Emdad DJ Volsky PB Fisher 2005 Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1 Gene 353 1 8 15 15927426 15927426
174. SG Lee HY Jeon ZZ Su JE Richards N Vozhilla D Sarkar T Van Maerken PB Fisher 2009 Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma Oncogene 28 26 2476 2484 19448665 19448665
175. H Liu X Song C Liu L Xie L Wei R Sun 2009 Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells J Exp Clin Cancer Res 28 19 19216799 19216799
176. A Ranki M Nyberg V Ovod M Haltia I Elovaara R Raininko H Haapasalo K Krohn 1995 Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia AIDS 9 9 1001 1008 8527071 8527071
177. S Kramer-Hammerle B Kohleisen C Hohenadl E Shumay I Becker V Erfle J Schmidt 2001 HIV type 1 Nef promotes neoplastic transformation of immortalized neural cells AIDS Res Hum Retrovir 17 7 597 602 11375055 11375055
178. EM Connor RS Sperling R Gelber, et al. 1994 Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group N Engl J Med 331 18 1173 1180 7935654
179. A Van Rie A Mupuala A Dow 2008 Impact of the HIV/AIDS epidemic on the neurodevelopment of preschool-aged children in Kinshasa, Democratic Republic of the Congo Pediatrics 122 1 e123 e128 18595957 18595957
180. GW Diamond J Kaufman AL Belman L Cohen HJ Cohen A Rubinstein 1987 Characterization of cognitive functioning in a subgroup of children with congenital HIV infection Arch Clin Neuropsychol 2 3 245 256 14589616 14589616
181. LG Epstein LR Sharer JM Oleske EM Connor J Goudsmit L Bagdon M Robert-Guroff MR Koenigsberger 1986 Neurologic manifestations of human immunodeficiency virus infection in children Pediatrics 78 4 678 687 2429248 2429248
182. RA Van PR Harrington A Dow K Robertson 2007 Neurologic and neurodevelopmental manifestations of pediatric HIV/AIDS: a global perspective Eur J Paediatr Neurol 11 1 1 9
183. AL Belman 1997 Pediatric neuro-AIDS. Update Neuroimaging Clin N Am 7 3 593 613 9376970
184. C Chase M Vibbert SI Pelton DL Coulter H Cabral 1995 Early neurodevelopmental growth in children with vertically transmitted human immunodeficiency virus infection Arch Pediatr Adolesc Med 149 8 850 855 7543334
185. R Smith K Malee R Leighty P Brouwers C Mellins J Hittelman C Chase I Blasini 2006 Effects of perinatal HIV infection and associated risk factors on cognitive development among young children Pediatrics 117 3 851 862 16510667
186. C Chase J Ware J Hittelman, et al. 2000 Early cognitive and motor development among infants born to women infected with human immunodeficiency virus. Women and Infants Transmission Study Group Pediatrics 106 2 E25 10920181
187. C Thorne ML Newell 2007 Safety of agents used to prevent mother-to-child transmission of HIV: is there any cause for concern? Drug Saf 30 3 203 213 17343429
188. M Bulterys S Nesheim EJ Abrams P Palumbo J Farley M Lampe MG Fowler 2000 Lack of evidence of mitochondrial dysfunction in the offspring of HIV-infected women. Retrospective review of perinatal exposure to antiretroviral drugs in the Perinatal AIDS Collaborative Transmission Study Ann NY Acad Sci 918 212 221 11131707
189. PL Williams M Marino K Malee S Brogly MD Hughes LM Mofenson 2010 Neurodevelopment and in utero antiretroviral exposure of HIV-exposed uninfected infants Pediatrics 125 2 e250 e260 20083530 20083530
190. Boksa P. Effects of prenatal infection on brain development and behavior: a review of findings from animal models; 2010; (1090-2139 (Electronic)).
191. JM Brenchley DA Price TW Schacker, et al. 2006 Microbial translocation is a cause of systemic immune activation in chronic HIV infection Nat Med 12 12 1365 1371 17115046
192. P Ancuta A Kamat KJ Kunstman, et al. 2008 Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients PLoS One 3 6 e2516 18575590 18575590
193. JL Teeling VH Perry 2009 Systemic Infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms Neuroscience 158 1062 1073 18706982
194. S Ahrne E Lonnermark AE Wold, et al. 2005 Lactobacilli in the intestinal microbiota of Swedish infants Microbes Infect 7 11-12 1256 1262 16002310
195. AE Wold I Adlerberth 2000 Breast feeding and the intestinal microflora of the infant-implications for protection against infectious diseases Adv Exp Med Biol 478 77 93 11065062
196. G Qing S Howlett R Bortolussi 1996 Lipopolysaccharide binding proteins on polymorphonuclear leukocytes: comparison of adult and neonatal cells Infect Immun 64 11 4638 4642 8890218
197. MA Wallet CA Rodriguez L Yin S Saporta S Chinratanapisit W Hou JW Sleasman MM Goodenow 2010 Microbial translocation induces persistent macrophage activation unrelated to HIV-1 levels or T-cell activation following therapy AIDS 24 9 1281 1290 20559035
198. DD Ho TR Rota RT Schooley, et al. 1985 Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome N Engl J Med 313 24 1493 1497 2999591 2999591
199. F Gonzalez-Scarano J Martin-Garcia 2005 The neuropathogenesis of AIDS Nat Rev Immunol 5 1 69 81 15630430 15630430
200. S Gartner 2000 HIV infection and dementia Science 287 5453 602 604 10691542 10691542
201. M Schwartz R Shechter 2010 Protective autoimmunity functions by intracranial immunosurveillance to support the mind: the missing link between health and disease Mol Psychiatry 15 342 354 20332793