Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons

Acta Neuropathologica

Volumn 125, Issue 4, 2013, Pages 595-608

  Singh, Shailender ^a,b   Metz, Imke ^a   Amor, Sandra ^b,c   Van Der Valk, Paul ^b   Stadelmann, Christine ^a   Brück, Wolfgang ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Axonal damage; Microglia activation; Microglial nodules; Multiple sclerosis; Preactive lesions; Wallerian degeneration

Indexed keywords

AMYLOID PRECURSOR PROTEIN; HLA ANTIBODY; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; NEUROPEPTIDE Y; NEUROPEPTIDE Y1 RECEPTOR;

ADULT; AGED; ARTICLE; BRAIN BIOPSY; CELL ACTIVATION; CLINICAL ARTICLE; CLINICAL FEATURE; CONTROLLED STUDY; DISEASE ASSOCIATION; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MICROGLIA; MULTIPLE SCLEROSIS; NERVE CELL DEGENERATION; NERVE CELL LESION; NERVE DEGENERATION; NEUROPATHOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; WHITE MATTER LESION;

ADULT; AGED; AMYLOID BETA-PROTEIN PRECURSOR; AXONS; BRAIN; FEMALE; HLA-DR ANTIGENS; HUMANS; MALE; MICROGLIA; MIDDLE AGED; MULTIPLE SCLEROSIS; NERVE FIBERS, MYELINATED; RECEPTORS, NEUROPEPTIDE Y; WALLERIAN DEGENERATION;

EID: 84876670276     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-013-1082-0     Document Type: Article

References (62)

1. Barnett MH, Parratt JD, Cho ES, Prineas JW (2009) Immunoglobulins and complement in postmortem multiple sclerosis tissue. Ann Neurol 65:32-46
2. Barnett MH, Prineas JW (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 55:458-468
3. Benveniste EN, Nguyen VT, Wesemann DR (2004) Molecular regulation of CD40 gene expression in macrophages and microglia. Brain Behav Immun 18(1):7-12
4. Bitsch A, da Costa C, Bunkowski S, Weber F, Rieckmann P, Brück W (1998) Identification of macrophage populations expressing tumor necrosis factor - a mRNA in acute multiple sclerosis. Acta Neuropathol 95:373-377
5. Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Brück W (2000) Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123:1174-1183
6. Bjartmar C, Kinkel PR, Kidd G, Rudick RA, Trapp BD (2001) Axonal loss in normal-appearing white matter in a patient with acute MS. Neurology 57:1248-1252
7. Bordey A, Spencer DD (2003) Chemokine modulation of high-conductance Ca(2 +)-sensitive K(+) currents in microglia from human hippocampi. Eur J Neurosci 18:2893-2898
8. Boven LA, Van Meurs M, Van Zwam M, Wierenga-Wolf A, Hintzen RQ, Boot RG, Aerts JM, Amor S, Nieuwenhuis EE, Laman JD (2006) Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis. Brain 129:517-526
9. Brück W, Porada P, Poser S, Rieckmann P, Hanefeld F, Kretzschmar HA, Lassmann H (1995) Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann Neurol 38:788-796
10. 1HMRS study. J Neurol 250:22-28
11. Ciccarelli O, Werring DJ, Barker GJ, Griffin CM, Wheeler-Kingshott CA, Miller DH, Thompson AJ (2003) A study of the mechanisms of normal-appearing white matter damage in multiple sclerosis using diffusion tensor imaging. Evidence of Wallerian degeneration. J Neurol 250:287-292
12. Corness J, Shi TJ, Xu ZQ, Brulet P, Hökfelt T (1996) Influence of leukemia inhibitory factor on galanin/GMAP and neuropeptide Y expression in mouse primary sensory neurons after axotomy. Exp Brain Res 112(1):79-88
13. De Groot CJA, Bergers E, Kamphorst W, Ravid R, Polman CH, Barkhof F, van der Valk P (2001) Post-mortem MRI-guided sampling of multiple sclerosis brain lesions. Increased yield of active demyelinating and (p)reactive lesions. Brain 124:1635-1645
14. De Stefano N, Narayanan S, Matthews PM, Francis GS, Antel JP, Arnold DL (1999) In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis. Brain 122:1933-1939
15. Dheen S, Kaur C, Ling E (2007) Microglial activation and its implications in the brain diseases. Curr Med Chem 14(11):1189-1197
16. Dissing-Olesen L, Ladeby R, Nielsen HH, Toft-Hansen H, Dalmau I, Finsen B (2007) Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse. Neuroscience 149:112-122
17. Dixon JE, Simpson A, Mistry N, Evangelou N, Morris PG (2011) Optimisation of T(2)-weighted MRI for the detection of small veins in multiple sclerosis at 3T and 7T. Eur J Radiol epub Eur J Radiol (Epub ahead of print 02 December 2011). doi: 10.1016/j.ejrad.2011.09.023
18. Dutta R, Trapp BD (2007) Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology 68:S22-S31
19. Dziedzic T, Metz I, Dallenga T, Konig FB, Muller S, Stadelmann C, Brück W (2010) Wallerian degeneration: a major component of early axonal pathology in multiple sclerosis. Brain Pathol 20:976-985
20. Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM (2000) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 47:391-395
21. Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120:393-399
22. Geddes JF (2005) Primary traumatic brain injury. In: Whitwell HL, Arnold E (eds) Forensic neuropathology, p 95-106
23. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23-35
24. Howell OW, Rundle JL, Garg A, Komada M, Brophy PJ, Reynolds R (2010) Activated microglia mediate axoglial disruption that contributes to axonal injury in multiple sclerosis. J Neuropathol Exp Neurol 69:1017-1033
25. Huizinga R, van der Star BJ, Kipp M, Jong R, Gerritsen W, Clarner T, Puentes F, Dijkstra CD, van der Valk P, Amor S (2012) Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis. Glia 60(3):422-431
26. Komohara Y, Hirahara J, Horikawa T, Kawamura K, Kiyota E, Sakashita N, Araki N, Takeya M (2006) AM-3 K, an anti-macrophage antibody, recognizes CD163, a molecule associated with an anti-inflammatory macrophage phenotype. J Histochem Cytochem 54(7):763-771
27. Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312-318
28. Kuhlmann T, Lassmann H, Brück W (2008) Diagnosis of inflammatory demyelination in biopsy specimens: a practical approach. Acta Neuropathol 115(3):275-287
29. Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Brück W (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125:2202-2212
30. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705-2712
31. Lassmann H (1998) Pathology of multiple sclerosis. In: Compston A, Ebers G, Lassmann H, McDonald I, Matthews B, Wekerle H (eds) McAlpine's multiple sclerosis. Churchill Livingstone, London, pp 323-358
32. Lassmann H, Kitz K, Wisniewski HM (1980) Structural variability of demyelinating lesions in different models of subacute and chronic experimental allergic encephalomyelitis. Acta Neuropathol 51:191-201
33. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707-717
34. Maeda A, Sobel RA (1996) Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J Neuropathol Exp Neurol 55:300-309
35. Mathey EK, Derfuss T, Storch MK, Williams KR, Hales K, Woolley DR, Al-Hayani A, Davies SN, Rasband MN, Olsson T, Moldenhauer A, Velhin S, Hohlfeld R, Meinl E, Linington C (2007) Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med 204:2363-2372
36. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121-127
37. Moll NM, Rietsch AM, Thomas S, Ransohoff AJ, Lee JC, Fox R, Chang A, Ransohoff RM, Fisher E (2011) Multiple sclerosis normal-appearing white matter: pathology-imaging correlations. Ann Neurol 70:764-773
38. Moreno B, Jukes JP, Vergara-Irigaray N, Errea O, Villoslada P, Perry VH, Newman TA (2011) Systemic inflammation induces axon injury during brain inflammation. Ann Neurol. 70:932-942
39. Newman TA, Woolley ST, Hughes PM, Sibson NR, Anthony DC, Perry VH (2001) T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases. Brain 124:2203-2214
40. Nikic I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Brück W, Bishop D, Misgeld T, Kerschensteiner M (2011) A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 17:495-499
41. Palin K, Cunningham C, Forse P, Perry VH, Platt N (2008) Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration. Neurobiol Dis 30:19-29
42. Pesini P, Kopp J, Wong H, Walsh JH, Grant G, Hökfelt T (1999) An immunohistochemical marker for Wallerian degeneration of fibers in the central and peripheral nervous system. Brain Res 828:41-59
43. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13(3):227-231
44. Prineas JW (1985) The neuropathology of multiple sclerosis. In: Vinken PJ, Bruyn GW, Klawans HL (eds) Handbook of clinical neurology. Elsevier Sciences, Amsterdam, pp 213-257
45. Prineas JW, Kwon EE, Cho ES, Sharer LR, Barnett MH, Oleszak EL, Hoffman B, Morgan BP (2001) Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol 50:646-657
46. Sanders V, Conrad AJ, Tourtellotte WW (1993) On classification of post-mortem multiple sclerosis plaques for neuroscientists. J Neuroimmunol 46:207-216
47. Shi F, Zhu H, Yang S, Liu Y, Feng Y, Shi J, Xu D, Wu W, You S, Ma Z, Zou J, Lu P, Xu XM (2009) Glial response and myelin clearance in areas of Wallerian degeneration after spinal cord hemisection in the monkey Macaca fascicularis. J Neurotrauma 26(11):2083-2096
48. Simon JH, Kinkel PR, Jacobs L, Bub L, Simonian N (2000) A Wallerian degeneration pattern in patients at risk for MS. Neurology 54:1155-1160
49. Smith KJ, Lassmann H (2002) The role of nitric oxide in multiple sclerosis. Lancet Neurol 1:232-241
50. Tallantyre EC, Morgan PS, Dixon JE, Al-Radaideh A, Brookes MJ, Evangelou N, Morris PG (2009) A comparison of 3T and 7T in the detection of small parenchymal veins within MS lesions. Invest Radiol 44:491-494
51. Thompson AJ, Montalban X, Barkhof F, Brochet B, Filippi M, Miller DH, Polman CH, Stevenson VL, McDonald WI (2000) Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol. 47(6):831-835
52. van der Valk P, De Groot CJA (2000) Review. Staging of multiple sclerosis (MS) lesions: pathology of the time frame of MS. Neuropathol Appl Neurobiol 26:2-10
53. van der Valk P, Amor S (2009) Preactive lesions in multiple sclerosis. Curr Opin Neurol 22:207-213
54. van Horssen J, Singh S, van der Pol S, Kipp M, Lim JL, Peferoen L, Gerritsen W, Kooi EJ, Witte ME, Geurts JJ, de Vries HE, Peferoen-Baert R, van den Elsen PJ, van der Valk P, Amor S (2012) Clusters of activated microglia in normal-appearing white matter show signs of innate immune activation. J Neuroinflammation 9(1):156
55. van Noort JM, Bsibsi M, Gerritsen WH, Van der Valk P, Bajramovic JJ, Steinman L, Amor S (2010) Alphab-crystallin is a target for adaptive immune responses and a trigger of innate responses in preactive multiple sclerosis lesions. J Neuropathol Exp Neurol 69:694-703
56. Vargas ME, Barres BA (2007) Why is Wallerian degeneration in the CNS so slow? Annu Rev Neurosci 30:153-179
57. Wakisaka S, Kajander KC, Bennett GJ (1991) Increased neuropeptide Y (NPY)-like immunoreactivity in rat sensory neurons following peripheral axotomy. Neurosci Lett 124(2):200-203
58. Wakisaka S, Kajander KC, Bennett GJ (1992) Effects of peripheral nerve injuries and tissue inflammation on the levels of neuropeptide Y-like immunoreactivity in rat primary afferent neurons. Brain Res 598(1-2):349-352
59. Werring DJ, Brassat D, Droogan AG, Clark CA, Symms MR, Barker GJ, MacManus DG, Thompson AJ, Miller DH (2000) The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis. A serial diffusion MRI study. Brain 123:1667-1676
60. Young NP, Weinshenker BG, Parisi JE, Scheithauer B, Giannini C, Roemer SF, Thomsen KM, Mandrekar JN, Erickson BJ, Lucchinetti CF (2010) Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis. Brain 133:333-348
61. Zhang X, Bao L, Xu ZQ, Kopp J, Arvidsson U, Elde R, Hökfelt T (1994) Localization of neuropeptide Y Y1 receptors in the rat nervous system with special reference to somatic receptors on small dorsal root ganglion neurons. Proc Natl Acad Sci USA 91(24):11738-11742
62. Zhang Z, Zhang ZY, Schittenhelm J, Wu Y, Meyermann R, Schluesener HJ (2011) Parenchymal accumulation of CD163 + macrophages/microglia in multiple sclerosis brains. J Neuroimmunol 237:73-79