Inflammation in CNS neurodegenerative diseases

Immunology

Volumn 154, Issue 2, 2018, Pages 204-219

  Stephenson, Jodie ^a,b   Nutma, Erik ^b   van der Valk, Paul ^b   Amor, Sandra ^a,b  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

immune response; inflammation; microbiome; neuroprotection; repair

Indexed keywords

ADAPTIVE IMMUNITY; AGING; CENTRAL NERVOUS SYSTEM DISEASE; DEGENERATIVE DISEASE; DISEASE COURSE; ENVIRONMENTAL FACTOR; HUMAN; IMMUNE PRIVILEGE; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; INFLAMMATION; INNATE IMMUNITY; LIFESTYLE; MICROBIOME; MICROGLIA; MONITORING; NERVE CELL; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NONHUMAN; OLIGODENDROGLIA; PRIORITY JOURNAL; REVIEW; RISK FACTOR; ANIMAL; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; COMPLICATION; ENVIRONMENT; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; MICROFLORA; PATHOLOGY;

ADAPTIVE IMMUNITY; AGING; ANIMALS; BLOOD-BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; ENVIRONMENT; HUMANS; IMMUNE PRIVILEGE; IMMUNITY, INNATE; IMMUNOTHERAPY; INFLAMMATION; LIFE STYLE; MICROBIOTA; NEURODEGENERATIVE DISEASES; RISK FACTORS;

EID: 85045585135     PISSN: 00192805     EISSN: 13652567     Source Type: Journal    
DOI: 10.1111/imm.12922     Document Type: Review

References (169)

1. Wimo A, Guerchet M, Ali GC, Wu YT, Prina AM, Winblad B et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement 2017; 13:1–7.
2. Cova I, Markova A, Campini I, Grande G, Mariani C, Pomati S. Worldwide trends in the prevalence of dementia. J Neurol Sci 2017; 379:259.
3. Perry VH. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun 2004; 18:407–13.
4. Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Incidence of epilepsy A systematic review and meta-analysis. Neurology 2011; 77:1005–12.
5. Singh A, Trevick S. The epidemiology of global epilepsy. Neurol Clin 2016; 34:837–47.
6. Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, Baker D et al. Inflammation in neurodegenerative diseases–an update. Immunology 2014; 142:151–66.
7. Mackenzie IS, Morant SV, Bloomfield GA, MacDonald TM, O'riordan J. Incidence and prevalence of multiple sclerosis in the UK 1990–2010: a descriptive study in the General Practice Research Database. J Neurol Neurosurg Psychiatry 2014; 85:76–84.
8. Myall DJ, Pitcher TL, Pearson JF, Dalrymple-Alford JC, Anderson TJ, MacAskill MR. Parkinson's in the oldest old: impact on estimates of future disease burden. Parkinsonism Relat Disord 2017; 42:78–84.
9. Tysnes OB, Storstein A. Epidemiology of Parkinson's disease. J Neural Transm 2017; 124:901–5.
10. Rawlins MD, Wexler NS, Wexler AR, Tabrizi SJ, Douglas I, Evans SJ et al. The prevalence of Huntington's disease. Neuroepidemiology 2016; 46:144–53.
11. Robertson A, Aartsma-Rus A, Jones CC, Lochmüller H, Wilson IJ, Verhaart IE et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy–a literature review. Orphanet J Rare Dis 2017; 12:124.
12. Chio A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA et al. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 2013; 41:118–30.
13. Arthur KC, Calvo A, Price TR, Geiger JT, Chio A, Traynor BJ. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun 2016; 7:12 408.
14. Mohan KM, Wolfe CD, Rudd AG, Heuschmann PU, Kolominsky-Rabas PL, Grieve AP. Risk and cumulative risk of stroke recurrence. Stroke 2011; 42:1489–94.
15. Stevens EGV, Emmet ES, Wang Y, McKevitt CJ, Wolfe CDA. The burden of stroke in Europe report King's college London. In Stroke Alliance for Europe. 2017 ISBN 0661.651.450, p 108.
16. Nguyen R, Fiest KM, McChesney J, Kwon CS, Jette N, Frolkis AD et al. The international incidence of traumatic brain injury: a systematic review and meta-analysis. Can J Neurol Sci 2016; 43:774–85.
17. UNAIDS (2017) Fact sheet 2017. URL http://www.unaids.org/en/resources/fact-sheet [accessed on 05 December 2017]
18. Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. Vaccine 2009; 27:B51–63.
19. Scott JG, Duhig M, Hamlyn J, Norman RE. Environmental contributions to autism: explaining the rise in incidence of autistic spectrum disorders. J Environ Immunol Toxicol 2014; 1:75–9.
20. Baxter AJ, Brugha TS, Erskine HE, Scheurer RW, Vos T, Scott JG. The epidemiology and global burden of autism spectrum disorders. Psychol Med 2015; 45:601–13.
21. Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T et al. Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med 2013; 43:471–81.
22. Hidaka BH. Depression as a disease of modernity: explanations for increasing prevalence. J Affect Disord 2012; 140:205–14.
23. Burns JK, Tomita A, Kapadia AS. Income inequality and schizophrenia: increased schizophrenia incidence in countries with high levels of income inequality. Int J Soc Psychiatry 2014; 60:185–96.
24. Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 2011; 68:241–51.
25. Yutzy SH, Woofter CR, Abbott CC, Melhem IM, Parish BS. The increasing frequency of mania and bipolar disorder: causes and potential negative impacts. J Nerv Ment Dis 2012; 200:380.
26. Wong CH, Jenne CN, Tam PP, Léger C, Venegas A, Ryckborst K et al. Prolonged activation of invariant natural killer T cells and TH2-skewed immunity in stroke patients. Front Neurol 2017; 8:6.
27. Zheng YH, Xiao SL, He B, He Y, Zhou HY, Chen Z et al. The role of IL-27 and its receptor in the pathogenesis of HIV/AIDS and anti-viral immune response. Curr HIV Res 2017; 15:279–84.
28. Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 2011; 62:141–55.
29. Ribes S, Nessler S, Heide EC, Malzahn D, Perske C, Brück W et al. The early adaptive immune response in the pathophysiology of pneumococcal meningitis. J Infect Dis 2017; 215:150–8.
30. Careaga M, Rogers S, Hansen RL, Amaral DG, Van de Water J, Ashwood P. Immune endophenotypes in children with autism spectrum disorder. Biol Psychiat 2017; 81:434–41.
31. Hughes MM, Connor TJ, Harkin A. Stress-related immune markers in depression: implications for treatment. Int J Neuropsychopharmacol 2016; 19:pii: pyw001.
32. Karpiński P, Frydecka D, Sąsiadek MM, Misiak B. Reduced number of peripheral natural killer cells in schizophrenia but not in bipolar disorder. Brain Behav Immun 2016; 54:194–200.
33. Kéri S, Szabó C, Kelemen O. Antipsychotics influence Toll-like receptor (TLR) expression and its relationship with cognitive functions in schizophrenia. Brain Behav Immun 2017; 62:256–64.
34. Ascoli BM, Géa LP, Colombo R, Barbé-Tuana FM, Kapczinski F, Rosa AR. The role of macrophage polarization on bipolar disorder: identifying new therapeutic targets. Aust N Z J Psychiatry 2016; 50:618–30.
35. Owens T, Bechmann I, Engelhardt B. Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol 2008; 67:1113–21.
36. Wilhelm I, Nyúl-Tóth Á, Suciu M, Hermenean A, Krizbai IA. Heterogeneity of the blood–brain barrier. Tissue Barriers 2016; 4:e1143544.
37. Iliff JJ, Nedergaard M. Is there a cerebral lymphatic system? Stroke 2013; 44(6 Suppl 1):S93–5.
38. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 2015; 212:991–9.
39. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015; 523:337–41.
40. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood–brain barrier. Neurobiol Dis 2010; 37:13–25.
41. Gorlé N, Van Cauwenberghe C, Libert C, Vandenbroucke RE. The effect of aging on brain barriers and the consequences for Alzheimer's disease development. Mamm Genome 2016; 27:407–20.
42. Bertram L. The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. Alzheimers Dement 2015; 1:10.
43. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012; 122:787.
44. Ruckh JM, Zhao JW, Shadrach JL, van Wijngaarden P, Rao TN, Wagers AJ et al. Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell 2012; 10:96–103.
45. Wes PD, Holtman IR, Boddeke EW, Möller T, Eggen BJ. Next generation transcriptomics and genomics elucidate biological complexity of microglia in health and disease. Glia 2016; 64:197–213.
46. Spangenberg EE, Lee RJ, Najafi AR, Rice RA, Elmore MR, Blurton-Jones M et al. Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-β pathology. Brain 2016; 139:1265–81.
47. Schaafsma W, Basterra LB, Jacobs S, Brouwer N, Meerlo P, Schaafsma A et al. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood. Neurobiol Dis 2017; 106:291–300.
48. Grabert K, Michoel T, Karavolos MH, Clohisey S, Baillie JK, Stevens MP et al. Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat Neurosci 2016; 19:504–16.
49. Erny D, de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 2015; 18:965–77.
50. Saederup N, Cardona AE, Croft K, Mizutani M, Cotleur AC, Tsou CL et al. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS ONE 2010; 5:e13693.
51. Zrzavy T, Hametner S, Wimmer I, Butovsky O, Weiner HL, Lassmann H. Loss of ‘homeostatic’ microglia and patterns of their activation in active multiple sclerosis. Brain 2017; 140:1900–13.
52. Liddelow SA, Barres BA. Reactive astrocytes: production, function, and therapeutic potential. Immunity 2017; 46:957–67.
53. Vilalta A, Brown GC. Neurophagy–the phagocytosis of live neurons and synapses by glia–contributes to brain development and disease. FEBS J 2017; https://doi.org/10.1111/febs.14323. [Epub ahead of print].
54. Eroglu C, Barres BA. Regulation of synaptic connectivity by glia. Nature 2010; 468:223–31.
55. Peferoen L, Kipp M, Valk P, Noort JM, Amor S. Oligodendrocyte-microglia cross-talk in the central nervous system. Immunology 2014; 141:302–13.
56. Gross CC, Schulte-Mecklenbeck A, Wiendl H, Marcenaro E, de Rosbo NK, Uccelli A et al. Regulatory functions of natural killer cells in multiple sclerosis. Front Immunol 2016; 7:606.
57. Suzuki H, Savitz J, Teague TK, Gandhapudi SK, Tan C, Misaki M et al. Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder: association with sleep disturbance. Brain Behav Immun 2017; 66:193–200.
58. Skaper SD, Facci L, Zusso M, Giusti P. Neuroinflammation, mast cells, and glia: dangerous liaisons. Neuroscientist 2017; 23:478–98.
59. Girolamo F, Coppola C, Ribatti D. Immunoregulatory effect of mast cells influenced by microbes in neurodegenerative diseases. Brain Behav Immun 2017; 65:68–89.
60. Elvington M, Liszewski MK, Atkinson JP. Evolution of the complement system: from defense of the single cell to guardian of the intravascular space. Immunol Rev 2016; 274:9–15.
61. McGeer PL, Lee M, McGeer EG. A review of human diseases caused or exacerbated by aberrant complement activation. Neurobiol Aging 2017; 52:12–22.
62. Bennett KM, Rooijakkers SH, Gorham RD Jr. Let's tie the knot: marriage of complement and adaptive immunity in pathogen evasion, for better or worse. Front Microbiol 2017; 8:89.
63. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG et al. Trained immunity: a program of innate immune memory in health and disease. Science 2016; 352:aaf1098.
64. Kalman B. Autoimmune encephalitides: a broadening field of treatable conditions. Neurologist 2017; 22:1–3.
65. Balint B, Vincent A, Meinck HM, Irani SR, Bhatia KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain 2018; 141:13–36.
66. Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J et al. T cells from patients with Parkinson's disease recognize α-synuclein peptides. Nature 2017; 546:656.
67. Beers DR, Zhao W, Wang J, Zhang X, Wen S, Neal D et al. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. JCI Insight 2017; 2:e89530.
68. Alves S, Churlaud G, Audrain M, Michaelsen-Preusse K, Fol R, Souchet B et al. Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer's disease mice. Brain 2017; 140:826–42.
69. Laurent C, Dorothée G, Hunot S, Martin E, Monnet Y, Duchamp M et al. Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy. Brain 2016; 140:184–200.
70. Wang F, Shen X, Li S, Chen L, Wang Y, Qin J et al. Splenocytes derived from young WT mice prevent AD progression in APPswe/PSENldE9 transgenic mice. Oncotarget 2015; 6:20 851.
71. Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman IL, Bryder D et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci USA 2010; 107:5465–70.
72. Castelo-Branco C, Soveral I. The immune system and aging: a review. Gynecol Endocrinol 2014; 30:16–22.
73. Olsson J, Wikby A, Johansson B, Löfgren S, Nilsson BO, Ferguson FG. Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev 2001; 121:187–201.
74. Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. EBioMedicine 2017; 16:41–50.
75. Vaknin-Dembinsky A, Karussis D, Avichzer J, Abramsky O. NMO spectrum of disorders: a paradigm for astrocyte-targeting autoimmunity and its implications for MS and other CNS inflammatory diseases. J Autoimmun 2014; 54:93–9.
76. Perry VH, Cunningham C, Holmes C. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 2007; 7:161–7.
77. Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med 2016; 8:343ra82.
78. Dinan TG, Cryan JF. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol 2017; 595:489–503.
79. Quigley EM. Microbiota-brain-gut axis and neurodegenerative diseases. Curr Neurol Neurosci Rep 2017; 17:94.
80. Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Soldan MM et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep 2016; 6:28 484.
81. Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A. Gut microbiota in autism and mood disorders. World J Gastroenterol 2016; 22:361.
82. Andreadou E, Pantazaki AA, Daniilidou M, Tsolaki M. Rhamnolipids, microbial virulence factors, in Alzheimer's disease. J Alzheimers Dis 2017; 59:209–22.
83. Goldman SM, Kamel F, Ross GW, Jewell SA, Marras C, Hoppin JA et al. Peptidoglycan recognition protein genes and risk of Parkinson's disease. Mov Disord 2014; 29:1171–80.
84. Berer K, Gerdes LA, Cekanaviciute E, Jia X, Xiao L, Xia Z et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci USA 2017; 114:10 719–24.
85. Cohen NA, Maharshak N. Novel indications for fecal microbial transplantation: update and review of the literature. Dig Dis Sci 2017; 62:131–1145.
86. Malek AM, Barchowsky A, Bowser R, Heiman-Patterson T, Lacomis D, Rana S et al. Environmental and occupational risk factors for amyotrophic lateral sclerosis: a case–control study. Neurodegener Dis 2014; 14:31–8.
87. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319:1668–72.
88. Seelen M, Campos RA, Veldink JH, Visser AE, Hoek G, Brunekreef B et al. Long-term air pollution exposure and amyotrophic lateral sclerosis in Netherlands: a population-based case–control study. Environ Health Perspect 2017; 125:1–7.
89. Jelinek GA, Marck CH, Weiland TJ, Pereira N, van der Meer DM, Hadgkiss EJ. Latitude, sun exposure and vitamin D supplementation: associations with quality of life and disease outcomes in a large international cohort of people with multiple sclerosis. BMC Neurol 2015; 15:132.
90. Block ML, Calderón-Garcidueñas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci 2009; 32:506–16.
91. Ingre C, Roos PM, Piehl F, Kamel F, Fang F. Risk factors for amyotrophic lateral sclerosis. Clin Epidemiol 2015; 7:181.
92. Campdelacreu J. Parkinson's disease and Alzheimer disease: environmental risk factors. Neurología 2014; 29:541–9.
93. Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Lancet Neurol 2015; 14:263–73.
94. Libbey JE, Cusick MF, Fujinami RS. Role of pathogens in multiple sclerosis. Int Rev Immunol 2014; 33:266–83.
95. Mettananda C, Rothwell P, Li L, Mehta Z, Gutnikov S. Comparison of risk factors for stroke subtypes versus acute coronary syndrome: a population-based study. In proceedings of the 17th Conference on Postgraduate Research, International Postgraduate Research Conference 2016, Faculty of Graduate Studies, University of Kelaniya, Sri Lanka. p 128.
96. Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Int J Epidemiol 2014; 43:443–64.
97. Chang SC, Pan A, Kawachi I, Okereke OI. Risk factors for late-life depression: a prospective cohort study among older women. Prev Med 2016; 91:144–51.
98. van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature 2010; 468:203–12.
99. Marangoni C, Hernandez M, Faedda GL. The role of environmental exposures as risk factors for bipolar disorder: a systematic review of longitudinal studies. J Affect Disord 2016; 193:165–74.
100. Duca LM, Beckham JD, Tyler KL, Pastula DM. Zika virus disease and associated neurologic complications. Curr Infect Dis Rep 2017; 19:4.
101. Billioux BJ. Neurological complications and sequelae of Ebola virus disease. Curr Infect Dis Rep 2017; 19:19.
102. Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E et al. Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000; 908:244–54.
103. Yankner BA, Lu T, Loerch P. The aging brain. Annu Rev Pathmechdis Mech Dis 2008; 3:41–66.
104. Rawji KS, Mishra MK, Michaels NJ, Rivest S, Stys PK, Yong VW. Immunosenescence of microglia and macrophages: impact on the ageing central nervous system. Brain 2016; 139:653–61.
105. Chinta SJ, Woods G, Rane A, Demaria M, Campisi J, Andersen JK. Cellular senescence and the aging brain. Exp Gerontol 2015; 68:3–7.
106. Spittau B. Aging microglia–phenotypes, functions and implications for age-related neurodegenerative diseases. Front Aging Neurosci 2017; 9:194.
107. Flanary BE, Sammons NW, Nguyen C, Walker D, Streit WJ. Evidence that aging and amyloid promote microglial cell senescence. Rejuvenation Res 2007; 10:61–74.
108. Franklin RJ, Zhao C, Sim FJ. Ageing and CNS remyelination. NeuroReport 2002; 13:923–8.
109. Albrecht DS, Granziera C, Hooker JM, Loggia ML. In vivo imaging of human neuroinflammation. ACS Chem Neurosci 2016; 7:470–83.
110. Kothur K, Wienholt L, Brilot F, Dale RC. CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: a systematic review. Cytokine 2016; 77:227–37.
111. El Ayoubi NK, Khoury SJ. Blood biomarkers as outcome measures in inflammatory neurologic diseases. Neurotherapeutics 2017; 14:135–47.
112. Croese T, Furlan R. Extracellular vesicles in neurodegenerative diseases. Mol Aspects Med 2017; 60:52–61.
113. Pulli B, Chen JW. Imaging neuroinflammation–from bench to bedside. J Clin Cell Immunol 2014; 5:pii: 226.
114. Zhang Y, Seeburg DP, Pulli B, Wojtkiewicz GR, Bure L, Atkinson W et al. Myeloperoxidase nuclear imaging for epileptogenesis. Radiology 2015; 278:822–30.
115. Petroni D, Giacomelli C, Taliani S, Barresi E, Robello M, Daniele S et al. Toward PET imaging of A 2B adenosine receptors: a carbon-11 labeled triazinobenzimidazole tracer: synthesis and imaging of a new A2B PET tracer. Nucl Med Biol 2016; 43:309–17.
116. Walsh AJ, Blevins G, Lebel RM, Seres P, Emery DJ, Wilman AH. Longitudinal MR imaging of iron in multiple sclerosis: an imaging marker of disease. Radiology 2014; 270:186–96.
117. Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and application in MR imaging. Eur J Radiol 2001; 11:2319–31.
118. Lue LF, Guerra A, Walker DG. Amyloid beta and tau as Alzheimer's disease blood biomarkers: promise from new technologies. Neurol Ther 2017; 6:25–36.
119. Heiss WD, Graf R, Fujita T, Ohta K, Bauer B, Löttgen J et al. Early detection of irreversibly damaged ischemic tissue by flumazenil positron emission tomography in cats. Stroke 1997; 28:2045–52.
120. Pascual B, Prieto E, Arbizu J, Marti-Climent JM, Peñuelas I, Quincoces G et al. Decreased carbon-11-flumazenil binding in early Alzheimer's disease. Brain 2012; 135:2817–25.
121. Freeman L, Garcia-Lorenzo D, Bottin L, Leroy C, Louapre C, Bodini B et al. The neuronal component of gray matter damage in multiple sclerosis: a [11C] flumazenil positron emission tomography study. Ann Neurol 2015; 78:554–67.
122. Juhasz C, Nagy F, Watson C, Da Silva EA, Muzik O, Chugani DC et al. Glucose and [11C] flumazenil positron emission tomography abnormalities of thalamic nuclei in temporal lobe epilepsy. Neurology 1999; 53:2037–45.
123. Serres S, Mardiguian S, Campbell SJ, McAteer MA, Akhtar A, Krapitchev A et al. VCAM-1-targeted magnetic resonance imaging reveals subclinical disease in a mouse model of multiple sclerosis. FASEB J 2011; 25:4415–22.
124. Gauberti M, Montagne A, Marcos-Contreras OA, Le Béhot A, Maubert E, Vivien D. Ultra-sensitive molecular MRI of vascular cell adhesion molecule-1 reveals a dynamic inflammatory penumbra after strokes. Stroke 2013; 44:1988–96.
125. Montagne A, Gauberti M, Macrez R, Jullienne A, Briens A, Raynaud JS et al. Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders. NeuroImage 2012; 63:760–70.
126. Chen JW, Breckwoldt MO, Aikawa E, Chiang G, Weissleder R. Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis. Brain 2008; 131:1123–33.
127. Breckwoldt MO, Chen JW, Stangenberg L, Aikawa E, Rodriguez E, Qiu S et al. Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci USA 2008; 105:18 584–9.
128. Costa GL, Sandora MR, Nakajima A, Nguyen EV, Taylor-Edwards C, Slavin AJ et al. Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit. J Immunol 2001; 167:2379–87.
129. Barrera P, Van der Laken CJ, Boerman OC, Oyen WJ, Van de Ven MT, Van Lent PL et al. Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients with rheumatoid arthritis. Rheumatology 2000; 39:870–4.
130. Wang C, Wu C, Popescu DC, Zhu J, Macklin WB, Miller RH et al. Longitudinal near-infrared imaging of myelination. J Neurosci 2011; 31:2382–90.
131. Frullano L, Wang C, Miller RH, Wang Y. A myelin-specific contrast agent for magnetic resonance imaging of myelination. J Am Chem Soc 2011; 133:1611–3.
132. O'Brien JT, Holmes C, Jones M, Jones R, Livingston G, McKeith I et al. Clinical practice with anti-dementia drugs: a revised (third) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol 2017; 31:147–68.
133. Brudek T, Winge K, Folke J, Christensen S, Fog K, Pakkenberg B et al. Autoimmune antibody decline in Parkinson's disease and Multiple System Atrophy; a step towards immunotherapeutic strategies. Mol Neurodegener 2017; 12:44.
134. Wyant KJ, Ridder AJ, Dayalu P. Huntington's disease–update on treatments. Curr Neurol Neurosci Rep 2017; 17:33.
135. Siniscalchi A, Iannacchero R, Anticoli S, Romana Pezzella F, De Sarro G, Gallelli L. Anti-inflammatory strategies in stroke: a potential therapeutic target. Curr Vasc Pharmacol 2016; 14:98–105.
136. Cortese I, Cornblath DR. Therapeutic plasma exchange in neurology: 2012. J Clin Apheresis 2013; 28:16–9.
137. Torkildsen Ø, Myhr KM, Bø L. Disease-modifying treatments for multiple sclerosis–a review of approved medications. Eur J Neurol 2016; 23(S1):18–27.
138. Wirth B, Barkats M, Martinat C, Sendtner M, Gillingwater TH. Moving towards treatments for spinal muscular atrophy: hopes and limits. Expert Opin Emerg Drugs 2015; 20:353–6.
139. Czarzasta J, Habich A, Siwek T, Czapliński A, Maksymowicz W, Wojtkiewicz J. Stem cells for ALS: an overview of possible therapeutic approaches. Int J Dev Neurosci 2017; 57:46–55.
140. Gros-Louis F, Soucy G, Larivière R, Julien JP. Intracerebroventricular infusion of monoclonal antibody or its derived Fab fragment against misfolded forms of SOD1 mutant delays mortality in a mouse model of ALS. J Neurochem 2010; 113:1188–99.
141. Pearn ML, Niesman IR, Egawa J, Sawada A, Almenar-Queralt A, Shah SB et al. Pathophysiology associated with traumatic brain injury: current treatments and potential novel therapeutics. Cell Mol Neurobiol 2017; 37:571–85.
142. Fong H, Tong LM, Huang Y. Stem cell therapy for Alzheimer's disease and related disorders: current status and future perspectives. Exp Mol Med 2015; 47:e151.
143. Shan Z, Hirai Y, Nakayama M, Hayashi R, Yamasaki T, Hasebe R et al. Therapeutic effect of autologous compact bone-derived mesenchymal stem cell transplantation on prion disease. J Gen Virol 2017; 98:2615–27.
144. Bhasin A, Srivastava MP, Mohanty S, Bhatia R, Kumaran SS, Bose S. Stem cell therapy: a clinical trial of stroke. Clin Neurol Neurosurg 2013; 115:1003–8.
145. Budni JL, Garcez M, Medeiros JD, Cassaro E, Bellettini-Santos T, Mina F et al. The anti-inflammatory role of minocycline in Alzheimer′s disease. Curr Alzheimer Res 2016; 13:1319–29.
146. Orsucci D, Calsolaro V, Mancuso M, Siciliano G. Neuroprotective effects of tetracyclines: molecular targets, animal models and human disease. CNS Neurol Disord Drug Targets 2009; 8:222–31.
147. Fattore L, ed. Cannabinoids in Neurologic and Mental Disease. United States of Amserica: Academic Press, 2015.
148. Pryce G, Riddall DR, Selwood DL, Giovannoni G, Baker D. Neuroprotection in experimental autoimmune encephalomyelitis and progressive multiple sclerosis by cannabis-based cannabinoids. J Neuroimmune Pharmacol 2015; 10:281–92.
149. Habib SS, Al-Regaiey K, Bashir S, Iqbal M. Role of endocannabinoids on neuroinflammation in autism spectrum disorder prevention. J Clin Diagn Res 2017; 11:CE01.
150. Martin K, Jackson CF, Levy RG, Cooper PN. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev 2016; 2:CD001903.
151. Ngo ST, Steyn FJ, McCombe PA. Body mass index and dietary intervention: implications for prognosis of amyotrophic lateral sclerosis. J Neurol Sci 2014; 340:5–12.
152. Otaegui-Arrazola A, Amiano P, Elbusto A, Urdaneta E, Martínez-Lage P. Diet, cognition, and Alzheimer's disease: food for thought. Eur J Nutr 2014; 53:1–23.
153. Perez-Pardo P, Dodiya HB, Broersen LM, Douna H, van Wijk N, Lopes da Silva S et al. Gut–brain and brain–gut axis in Parkinson's disease models: effects of a uridine and fish oil diet. Nutr Neurosci 2017; https://doi.org/10.1080/1028415X.2017.1294555. [Epub ahead of print]
154. Komori T. The significance of proinflammatory cytokines and Th1/Th2 balance in depression and action of antidepressants. Neuropsychiatry 2017; 7:57–60.
155. Moreno JA, Halliday M, Molloy C, Radford H, Verity N, Axten JM et al. Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci Transl Med 2013; 5:206ra138.
156. Berkovic SF. Epilepsy research in 2016: new treatment directions. Lancet Neurol 2017; 16:7.
157. Yang AC, Tsai SJ. New targets for schizophrenia treatment beyond the dopamine hypothesis. Int J Mol Sci 2017; 18:1689.
158. Rosenblat JD, Kakar R, Berk M, Kessing LV, Vinberg M, Baune BT et al. Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. Bipolar Disord 2016; 18:89–101.
159. Williams UE, Philip-Ephraim EE, Oparah SK. Multidisciplinary interventions in motor neuron disease. J Neurodegener Dis 2014; 2014:435 164.
160. Cai Z, Liu N, Wang C, Qin B, Zhou Y, Xiao M et al. Role of RAGE in Alzheimer's disease. Cell Mol Neurobiol 2016; 36:483–95.
161. Alawieh A, Tomlinson S. Injury site-specific targeting of complement inhibitors for treating stroke. Immunol Rev 2016; 274:270–80.
162. Fluiter K, Opperhuizen AL, Morgan BP, Baas F, Ramaglia V. Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. J Immunol 2014; 192:2339–48.
163. Liguori C, Romigi A, Izzi F, Placidi F, Nuccetelli M, Cordella A et al. Complement system dysregulation in patients affected by idiopathic generalized epilepsy and the effect of antiepileptic treatment. Epilepsy Res 2017; 137:107–11.
164. Dey A, Kang X, Qiu J, Du Y, Jiang J. Anti-inflammatory small molecules to treat seizures and epilepsy: from bench to bedside. Trends Pharmacol Sci 2016; 37:463–84.
165. Zhao P, Yang X, Yang L, Li M, Wood K, Liu Q et al. Neuroprotective effects of fingolimod in mouse models of Parkinson's disease. FASEB J 2017; 31:172–9.
166. Lundberg C, Bjorklund T, Carlsson T, Jakobsson J, Hantraye P, Déglon N et al. Applications of lentiviral vectors for biology and gene therapy of neurological disorders. Curr Gene Ther 2008; 8:461–73.
167. Safety T. Pharmacokinetics and pharmacodynamics of IONIS-HTTRx in patients with early manifest Huntington's disease. NCT02519036. 2015.
168. Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med 2017; 377:1630–8.
169. van Noort JM, Bsibsi M, Nacken PJ, Verbeek R, Venneker EH. Therapeutic intervention in multiple sclerosis with alpha B-crystallin: a randomized controlled phase IIa trial. PLoS ONE 2015; 10:e0143366.