Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Multiple Sclerosis | Research

Dynamic response of microglia/macrophage polarization following demyelination in mice

Authors: Tianci Chu, Yi Ping Zhang, Zhisen Tian, Chuyuan Ye, Mingming Zhu, Lisa B. E. Shields, Maiying Kong, Gregory N. Barnes, Christopher B. Shields, Jun Cai

Published in: Journal of Neuroinflammation | Issue 1/2019

Login to get access

Abstract

Background

The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process.

Methods

The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases.

Results

The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function.

Conclusions

This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.
Appendix
Available only for authorised users
Literature
1.
Franklin RJ, Ffrench-Constant C. Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci. 2008;9:839–55.PubMedCrossRef
2.
Smith KJ, Blakemore WF, McDonald WI. Central remyelination restores secure conduction. Nature. 1979;280:395–6.PubMedCrossRef
3.
Funfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012;485:517–21.PubMedPubMedCentralCrossRef
4.
Patani R, Balaratnam M, Vora A, Reynolds R. Remyelination can be extensive in multiple sclerosis despite a long disease course. Neuropathol Appl Neurobiol. 2007;33:277–87.PubMedCrossRef
5.
Boyd A, Zhang H, Williams A. Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models. Acta Neuropathol. 2013;125:841–59.PubMedPubMedCentralCrossRef
6.
Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, et al. Remyelination is extensive in a subset of multiple sclerosis patients. Brain. 2006;129:3165–72.PubMedCrossRef
7.
Raine CS, Wu E. Multiple sclerosis: remyelination in acute lesions. J Neuropathol Exp Neurol. 1993;52:199–204.PubMedCrossRef
8.
Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES. Multiple sclerosis: remyelination of nascent lesions. Ann Neurol. 1993;33:137–51.PubMedCrossRef
9.
Chang A, Tourtellotte WW, Rudick R, Trapp BD. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med. 2002;346:165–73.PubMedCrossRef
10.
Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain. 1999;122(Pt 12):2279–95.PubMedCrossRef
11.
Nataf S. Neuroinflammation responses and neurodegeneration in multiple sclerosis. Rev Neurol (Paris). 2009;165:1023–8.CrossRef
12.
13.
Cash E, Zhang Y, Rott O. Microglia present myelin antigens to T cells after phagocytosis of oligodendrocytes. Cell Immunol. 1993;147:129–38.PubMedCrossRef
14.
Kotter MR, Zhao C, van Rooijen N, Franklin RJ. Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression. Neurobiol Dis. 2005;18:166–75.PubMedCrossRef
15.
Olah M, Amor S, Brouwer N, Vinet J, Eggen B, Biber K, et al. Identification of a microglia phenotype supportive of remyelination. Glia. 2012;60:306–21.PubMedCrossRef
16.
Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013;16:1211–8.PubMedPubMedCentralCrossRef
17.
Li WW, Setzu A, Zhao C, Franklin RJ. Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination. J Neuroimmunol. 2005;158:58–66.PubMedCrossRef
18.
19.
Foote AK, Blakemore WF. Inflammation stimulates remyelination in areas of chronic demyelination. Brain. 2005;128:528–39.PubMedCrossRef
20.
Huitinga I, van Rooijen N, de Groot CJ, Uitdehaag BM, Dijkstra CD. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med. 1990;172:1025–33.PubMedCrossRef
21.
Brosnan CF, Bornstein MB, Bloom BR. The effects of macrophage depletion on the clinical and pathologic expression of experimental allergic encephalomyelitis. J Immunol. 1981;126:614–20.PubMed
22.
Edwards JP, Zhang X, Frauwirth KA, Mosser DM. Biochemical and functional characterization of three activated macrophage populations. J Leukoc Biol. 2006;80:1298–307.PubMedCrossRef
23.
Miller RH, Fyffe-Maricich S, Caprariello AC. Animal models for the study of multiple sclerosis. In: Conn PM, editor. Animal models for the study of human disease. 2nd ed; 2017. p. 967–88.CrossRef
24.
Zhang Y, Zhang YP, Pepinsky B, Huang G, Shields LB, Shields CB, et al. Inhibition of LINGO-1 promotes functional recovery after experimental spinal cord demyelination. Exp Neurol. 2015;266:68–73.PubMedCrossRef
25.
Gu Z, Li F, Zhang YP, Shields LB, Hu X, Zheng Y, et al. Apolipoprotein E mimetic promotes functional and histological recovery in lysolecithin-induced spinal cord demyelination in mice. J Neurol Neurophysiol. 2013;2014:10.PubMed
26.
Felts PA, Woolston AM, Fernando HB, Asquith S, Gregson NA, Mizzi OJ, et al. Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide. Brain. 2005;128:1649–66.PubMedCrossRef
27.
Blakemore WF, Franklin RJ. Remyelination in experimental models of toxin-induced demyelination. Curr Top Microbiol Immunol. 2008;318:193–212.PubMed
28.
Hall SM. The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci. 1972;10:535–46.PubMed
29.
Jeffery ND, Blakemore WF. Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin. J Neurocytol. 1995;24:775–81.PubMedCrossRef
30.
Fancy SP, Baranzini SE, Zhao C, Yuk DI, Irvine KA, Kaing S, et al. Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev. 2009;23:1571–85.PubMedPubMedCentralCrossRef
31.
Lau LW, Keough MB, Haylock-Jacobs S, Cua R, Doring A, Sloka S, et al. Chondroitin sulfate proteoglycans in demyelinated lesions impair remyelination. Ann Neurol. 2012;72:419–32.PubMedCrossRef
32.
Desai RA, Davies AL, Tachrount M, Kasti M, Laulund F, Golay X, et al. Cause and prevention of demyelination in a model multiple sclerosis lesion. Ann Neurol. 2016;79:591–604.PubMedPubMedCentralCrossRef
33.
Marik C, Felts PA, Bauer J, Lassmann H, Smith KJ. Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity? Brain. 2007;130:2800–15.PubMedCrossRef
34.
Wang Y, Gao Z, Zhang Y, Feng S-Q, Liu Y, Shields LBE, et al. Attenuated reactive gliosis and enhanced functional recovery following spinal cord injury in null mutant mice of platelet-activating factor receptor. Mol Neurobiol. 2015;53:3448–61.PubMedCrossRef
35.
Cai J, Zhu Q, Zheng K, Li H, Qi Y, Cao Q, et al. Co-localization of Nkx6.2 and Nkx2.2 homeodomain proteins in differentiated myelinating oligodendrocytes. Glia. 2010;58:458–68.PubMedPubMedCentral
36.
Cai J, Qi Y, Hu X, Tan M, Liu Z, Zhang J, et al. Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron. 2005;45:41–53.PubMedCrossRef
37.
Chu T, Zhou H, Wang T, Lu L, Li F, Liu B, et al. In vitro characteristics of valproic acid and all-trans-retinoic acid and their combined use in promoting neuronal differentiation while suppressing astrocytic differentiation in neural stem cells. Brain Res. 2015;1596:31–47.PubMedCrossRef
38.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.CrossRefPubMed
39.
Kozlowski P, Raj D, Liu J, Lam C, Yung AC, Tetzlaff W. Characterizing white matter damage in rat spinal cord with quantitative MRI and histology. J Neurotrauma. 2008;25:653–76.PubMedCrossRef
40.
41.
Concha L. A macroscopic view of microstructure: using diffusion-weighted images to infer damage, repair, and plasticity of white matter. Neuroscience. 2014;276:14–28.PubMedCrossRef
42.
Kim JH, Song S-K. Diffusion tensor imaging of the mouse brainstem and cervical spinal cord. Nat Protoc. 2013;8:409–17.PubMedCrossRef
43.
Ansari MK, Yong HY, Metz L, Yong VW, Zhang Y. Changes in tissue directionality reflect differences in myelin content after demyelination in mice spinal cords. J Struct Biol. 2014;188:116–22.PubMedCrossRef
44.
Wang G, Zhang YP, Gao Z, Shields LBE, Li F, Chu T, et al. Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury. Dis Model Mech. 2018;11:dmm030387.CrossRef
45.
Stanley JL, Lincoln RJ, Brown TA, McDonald LM, Dawson GR, Reynolds DS. The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines. J Psychopharmacol. 2005;19:221–7.PubMedCrossRef
46.
Boehm SL 2nd, Schafer GL, Phillips TJ, Browman KE, Crabbe JC. Sensitivity to ethanol-induced motor incoordination in 5-HT (1B) receptor null mutant mice is task-dependent: implications for behavioral assessment of genetically altered mice. Behav Neurosci. 2000;114:401–9.PubMedCrossRef
47.
Piot-Grosjean O, Wahl F, Gobbo O, Stutzmann JM. Assessment of sensorimotor and cognitive deficits induced by a moderate traumatic injury in the right parietal cortex of the rat. Neurobiol Dis. 2001;8:1082–93.PubMedCrossRef
48.
Carter RJ, Morton J, Dunnett SB. Motor coordination and balance in rodents. Curr Protoc Neurosci. 2001;15:8.12.1–8.4.CrossRef
49.
Luong TN, Carlisle HJ, Southwell A, Patterson PH. Assessment of motor balance and coordination in mice using the balance beam. J Vis Exp. 2011;49:e2376.
50.
Arfanakis K, Haughton VM, Carew JD, Rogers BP, Dempsey RJ, Meyerand ME. Diffusion tensor MR imaging in diffuse axonal injury. AJNR Am J Neuroradiol. 2002;23:794–802.PubMedPubMedCentral
51.
Beaulieu C, Does MD, Snyder RE, Allen PS. Changes in water diffusion due to Wallerian degeneration in peripheral nerve. Magn Reson Med. 1996;36:627–31.PubMedCrossRef
52.
Dijkhuizen RM, de Graaf RA, Tulleken KA, Nicolay K. Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain. J Cereb Blood Flow Metab. 1999;19:341–9.PubMedCrossRef
53.
Hinkle DE, Wiersma W, Jurs SG. Applied statistics for the behavioral sciences. 5th ed. Boston: Houghton Mifflin; 2003.
54.
Mukaka MM. Statistics corner: a guide to appropriate use of correlation coefficient in medical research. Malawi Med J. 2012;24:69–71.PubMedPubMedCentral
55.
Popescu BF, Pirko I, Lucchinetti CF. Pathology of multiple sclerosis: where do we stand? Continuum (Minneap Minn). 2013;19:901–21.
56.
Crawford AH, Chambers C, Franklin RJ. Remyelination: the true regeneration of the central nervous system. J Comp Pathol. 2013;149:242–54.PubMedCrossRef
57.
58.
Rudick RA, Ransohoff RM. Cytokine secretion by multiple sclerosis monocytes. Relationship to disease activity. Arch Neurol. 1992;49:265–70.PubMedCrossRef
59.
Payne SC, Bartlett CA, Harvey AR, Dunlop SA, Fitzgerald M. Myelin sheath decompaction, axon swelling, and functional loss during chronic secondary degeneration in rat optic nerve. Invest Ophthalmol Vis Sci. 2012;53:6093–101.PubMedCrossRef
60.
Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988;23:339–46.PubMedCrossRef
61.
Rossi S, Furlan R, De Chiara V, Motta C, Studer V, Mori F, et al. Interleukin-1beta causes synaptic hyperexcitability in multiple sclerosis. Ann Neurol. 2012;71:76–83.PubMedCrossRef
62.
Ferrari CC, Pott Godoy MC, Tarelli R, Chertoff M, Depino AM, Pitossi FJ. Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra. Neurobiol Dis. 2006;24:183–93.PubMedCrossRef
63.
Rossi S, Studer V, Motta C, Germani G, Macchiarulo G, Buttari F, et al. Cerebrospinal fluid detection of interleukin-1beta in phase of remission predicts disease progression in multiple sclerosis. J Neuroinflammation. 2014;11:32.PubMedPubMedCentralCrossRef
64.
Ferrari CC, Depino AM, Prada F, Muraro N, Campbell S, Podhajcer O, et al. Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain. Am J Pathol. 2004;165:1827–37.PubMedPubMedCentralCrossRef
65.
Rollnik JD, Sindern E, Schweppe C, Malin JP. Biologically active TGF-beta 1 is increased in cerebrospinal fluid while it is reduced in serum in multiple sclerosis patients. Acta Neurol Scand. 1997;96:101–5.PubMedCrossRef
66.
Gveric D, Cuzner ML, Newcombe J. Insulin-like growth factors and binding proteins in multiple sclerosis plaques. Neuropathol Appl Neurobiol. 1999;25:215–25.PubMedCrossRef
67.
Wilczak N, Schaaf M, Bredewold R, Streefland C, Teelken A, De Keyser J. Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis. Neurosci Lett. 1998;257:168–70.PubMedCrossRef
68.
69.
McKinnon RD, Piras G, Ida JA Jr, Dubois-Dalcq M. A role for TGF-beta in oligodendrocyte differentiation. J Cell Biol. 1993;121:1397–407.PubMedCrossRef
70.
Liu X, Yao DL, Webster H. Insulin-like growth factor I treatment reduces clinical deficits and lesion severity in acute demyelinating experimental autoimmune encephalomyelitis. Mult Scler. 1995;1:2–9.PubMedCrossRef
71.
Yao DL, Liu X, Hudson LD, Webster HD. Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1995;92:6190–4.PubMedPubMedCentralCrossRef
72.
73.
Patel JR, Williams JL, Muccigrosso MM, Liu L, Sun T, Rubin JB, et al. Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS. Acta Neuropathol. 2012;124:847–60.PubMedPubMedCentralCrossRef
74.
Hauser SL, Doolittle TH, Lincoln R, Brown RH, Dinarello CA. Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology. 1990;40:1735–9.PubMedCrossRef
75.
Brogi A, Strazza M, Melli M, Costantino-Ceccarini E. Induction of intracellular ceramide by interleukin-1 beta in oligodendrocytes. J Cell Biochem. 1997;66:532–41.PubMedCrossRef
76.
Merrill JE. Effects of interleukin-1 and tumor necrosis factor-alpha on astrocytes, microglia, oligodendrocytes, and glial precursors in vitro. Dev Neurosci. 1991;13:130–7.PubMedCrossRef
77.
Schonberg DL, Popovich PG, McTigue DM. Oligodendrocyte generation is differentially influenced by toll-like receptor (TLR) 2 and TLR4-mediated intraspinal macrophage activation. J Neuropathol Exp Neurol. 2007;66:1124–35.PubMedCrossRef
78.
Suzumura A, Takeuchi H, Zhang G, Kuno R, Mizuno T. Roles of glia-derived cytokines on neuronal degeneration and regeneration. Ann N Y Acad Sci. 2006;1088:219–29.PubMedCrossRef
79.
Herx LM, Rivest S, Yong VW. Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 beta is required for the production of ciliary neurotrophic factor. J Immunol. 2000;165:2232–9.PubMedCrossRef
80.
81.
Arnett HA, Mason J, Marino M, Suzuki K, Matsushima GK, Ting JP. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 2001;4:1116–22.PubMedCrossRef
82.
Moyon S, Dubessy AL, Aigrot MS, Trotter M, Huang JK, Dauphinot L, et al. Demyelination causes adult CNS progenitors to revert to an immature state and express immune cues that support their migration. J Neurosci. 2015;35:4–20.PubMedPubMedCentralCrossRef
83.
Mason JL, Ye P, Suzuki K, D'Ercole AJ, Matsushima GK. Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J Neurosci. 2000;20:5703–8.PubMedPubMedCentralCrossRef
84.
Mason JL, Jones JJ, Taniike M, Morell P, Suzuki K, Matsushima GK. Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte progenitor accumulation and differentiation during demyelination/remyelination. J Neurosci Res. 2000;61:251–62.PubMedCrossRef
85.
Mitchell K, Shah JP, Tsytsikova LV, Campbell AM, Affram K, Symes AJ. LPS antagonism of TGF-beta signaling results in prolonged survival and activation of rat primary microglia. J Neurochem. 2014;129:155–68.PubMedCrossRef
86.
87.
Zhou X, Spittau B, Krieglstein K. TGFbeta signalling plays an important role in IL4-induced alternative activation of microglia. J Neuroinflammation. 2012;9:210.PubMedPubMedCentralCrossRef
88.
Spittau B, Wullkopf L, Zhou X, Rilka J, Pfeifer D, Krieglstein K. Endogenous transforming growth factor-beta promotes quiescence of primary microglia in vitro. Glia. 2013;61:287–300.PubMedCrossRef
89.
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.PubMedPubMedCentralCrossRef
90.
Esiri MM, Reading MC. Macrophage populations associated with multiple sclerosis plaques. Neuropathol Appl Neurobiol. 1987;13:451–65.PubMedCrossRef
91.
Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in acute multiple sclerosis lesions. Brain. 1997;120(Pt 3):393–9.PubMedCrossRef
92.
Prineas JW, Kwon EE, Cho ES, Sharer LR, Barnett MH, Oleszak EL, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50:646–57.PubMedCrossRef
93.
Vogel DY, Vereyken EJ, Glim JE, Heijnen PD, Moeton M, van der Valk P, et al. Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status. J Neuroinflammation. 2013;10:35.PubMedPubMedCentralCrossRef
94.
Dunn SE, Gunde E, Lee H. Sex-based differences in multiple sclerosis (MS): part II: rising incidence of multiple sclerosis in women and the vulnerability of men to progression of this disease. Curr Top Behav Neurosci. 2015;26:57–86.PubMedCrossRef
95.
Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 2010;9:520–32.PubMedCrossRef
96.
Ribbons KA, McElduff P, Boz C, Trojano M, Izquierdo G, Duquette P, et al. Male sex is independently associated with faster disability accumulation in relapse-onset MS but not in primary progressive MS. PLoS One. 2015;10:e0122686.PubMedPubMedCentralCrossRef
97.
Pelfrey CM, Cotleur AC, Lee JC, Rudick RA. Sex differences in cytokine responses to myelin peptides in multiple sclerosis. J Neuroimmunol. 2002;130:211–23.PubMedCrossRef
98.
Papenfuss TL, Rogers CJ, Gienapp I, Yurrita M, McClain M, Damico N, et al. Sex differences in experimental autoimmune encephalomyelitis in multiple murine strains. J Neuroimmunol. 2004;150:59–69.PubMedCrossRef
99.
Voskuhl RR, Pitchekian-Halabi H, MacKenzie-Graham A, McFarland HF, Raine CS. Gender differences in autoimmune demyelination in the mouse: implications for multiple sclerosis. Ann Neurol. 1996;39:724–33.PubMedCrossRef
100.
Cerghet M, Skoff RP, Bessert D, Zhang Z, Mullins C, Ghandour MS. Proliferation and death of oligodendrocytes and myelin proteins are differentially regulated in male and female rodents. J Neurosci. 2006;26:1439–47.PubMedPubMedCentralCrossRef
101.
102.
Swamydas M, Bessert D, Skoff R. Sexual dimorphism of oligodendrocytes is mediated by differential regulation of signaling pathways. J Neurosci Res. 2009;87:3306–19.PubMedPubMedCentralCrossRef
103.
Rettew JA, Huet-Hudson YM, Marriott I. Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod. 2008;78:432–7.PubMedCrossRef
Metadata
Title
Dynamic response of microglia/macrophage polarization following demyelination in mice
Authors
Tianci Chu
Yi Ping Zhang
Zhisen Tian
Chuyuan Ye
Mingming Zhu
Lisa B. E. Shields
Maiying Kong
Gregory N. Barnes
Christopher B. Shields
Jun Cai
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1586-1

Other articles of this Issue 1/2019

Journal of Neuroinflammation 1/2019 Go to the issue

Research

Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer’s disease

Research

LncRNA-1810034E14Rik reduces microglia activation in experimental ischemic stroke

Research

Osteopontin and its spatiotemporal relationship with glial cells in the striatum of rats treated with mitochondrial toxin 3-nitropropionic acid: possible involvement in phagocytosis

Research

Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation

Letter to the Editor

Plasma VCAM1 levels correlate with disease severity in Parkinson’s disease

Research

The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders