The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
The Neurotoxicant, Cuprizone, as a Model to Study Demyelination and Remyelination in the Central Nervous System
Open accessAbstract
Myelin of the adult CNS is vulnerable to a variety of metabolic, toxic, and autoimmune insults. That remyelination can ensue, following demyelinating insult, has been well demonstrated. Details of the process of remyelination are, however difficult to ascertain since in most experimental models of demyelination/remyelination the severity, localization of lesion site, or time course of the pathophysiology is variable from animal to animal. In contrast, an experimental model in which massive demyelination can be reproducibly induced in large areas of mouse brain is exposure to the copper chelator, cuprizone, in the diet. We review work from several laboratories over the past 3 decades, with emphasis on our own recent studies, which suggest an overall picture of cellular events involved in demyelination/remyelination. When 8 week old C57BL/6 mice are fed 0.2% cuprizone in the diet, mature olidgodendroglia are specifically insulted (cannot fulfill the metabolic demand of support of vast amounts of myelin) and go through apoptosis.This is closely followed by recruitment of microglia and phagoctytosis of myelin. Studies of myelin gene expression, coordinated with morphological studies, indicate that even in the face of continued metabolic challenge, oligodendroglial progenitor cells proliferate and invade demyelinated areas. If the cuprizone challenge is terminated, an almost complete remyelination takes place in a matter of weeks. Communication between different cell types by soluble factors may be inferred. This material is presented in the context of a model compatible with present data—and which can be tested more rigorously with the cuprizone model. The reproducibility of the model indicates that it may allow for testing of manipulations (e.g. available knockouts or transgenics on the common genetic background, or pharmacological treatments) which may accelerate or repress the process of demyelination and or remyelination.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The C57BL/6 mice showed a dramatic loss of myelin staining at this time point (Fig. 1b), which is consistent with previous reports [5].”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Upon treatment with cuprizone, mice typically exhibit profound demyelination in the corpus callosum, the cortex and the superior cerebellar peduncles [4, 5].”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Most investigators use the standard C57BL/6 mouse strain in the cuprizone model to study the different molecular components involved in the complex pathogenic processes leading to corpus callosum demyelination [5].”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the corpus callosum, apoptosis of oligodendrocytes is observed, together with recruitment of microglia/macrophages, astrocytes and oligodendrocyte progenitor cells (OPCs) [5, 6].”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In contrast, the continuous exposure of C57BL/6 mice to cuprizone results in a pattern of two cycles of demyelination and remyelination, followed by chronic demyelination from which animals do not recover 36, 39.”
From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [39]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, C57BL/6 mice experience a spontaneous partial remyelination after 6 weeks and then continue to demyelinate further when exposed continuously to cuprizone 36, 39.”
From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thus, unlike microglia and astrocytes in C57BL/6 mice that respond vigorously to demyelination 2, 23, 39, these cell types in SJL mice have a guarded response at midline and in the lateral region, which correlates with subdued demyelination.”
From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Cuprizone toxicity produces profound demyelination in the white and grey matter of the brain that mirrors sites of MS pathology [46].”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Other features common to both cuprizone-induced and type 3 MS lesions are mitochondrial stress, selective loss of myelin-associated glycoprotein (MAG), lesions with indistinct borders that are not perivascular, pronounced glial activation, and lymphocyte infiltration [43, 46, 65, 69–71].”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The histopathological hallmark of the cuprizone model as standardized by Hiremath is oligodendrocyte death and subsequent demyelination in the corpus callosum, superior cerebellar peduncles, hippocampus [42, 46–54] and several other areas of the mouse brain (reviewed in [20]).”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microglial activation and axonal loss positively correlate with demyelination and the reproducible lesion localization – primarily in the corpus callosum [186], cerebellar peduncle [186], hippocampus [187], and cortex [184, 185, 188] – mirrors the topographical specificity of MS pathology, including subpial cortical demyelination seen in PMS patients.”
From Insights and challenges on animal models for progressive multiple sclerosis (2026) · cites this paper as [186]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Remyelination is very robust in the cuprizone model and starts directly after demyelination is complete, irrespective if cuprizone is further fed or not (Matsushima and Morell, 2001; Hiremath et al., 2008; Gudi et al., 2009).”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Matsushima and Morell, 2001
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Depletion of microglia likewise prevented the loss of oligodendrocytes (OLs) in the CC that normally results from CUP treatment (Matsushima & Morell, 2001).”
From Activated microglia drive demyelination via CSF1R signaling (2021) · cites this paper as Matsushima & Morell, 2001
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The cuprizone model involves administration of the toxin cuprizone to induce oligodendrocyte apoptosis [4, 5].”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“Here, we explored the effect of antibody-mediated TREM2 activation on microglia in a well-established toxin-induced model of demyelination in the CNS resulting from exposure to the copper chelator cuprizone (CPZ) in the diet [31].”
From TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis (2020) · cites this paper as [31]
The cited source says what the claim attributes to it.
In the citing paper
“These events lead to OPC recruitment, differentiation into mature OLs, and then remyelination which is almost complete within few weeks from toxin withdrawal [31].”
From TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis (2020) · cites this paper as [31]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“It may suggest that NODDI could be sensitive biomarkers to probe the different stages of white matter pathology between acute demyelination and chronic demyelination (Matsushima and Morell 2001).”
From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Matsushima and Morell 2001
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Historically these cells are not linked to demyelination following cuprizone treatment because the loss of the V(D)J recombination activation gene-1 (RAG-1), which is critical for B- and T- lymphocyte generation [269], does not alter demyelination and T-cell accumulation in the corpus callosum [46, 270].”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [46]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Demyelination peaks between 4.5 and 5 weeks of cuprizone exposure in the CC and between 5 and 6 weeks in the cortex and hippocampus (Hiremath et al., 1998; Matsushima and Morell, 2001; Skripuletz et al., 2008; Gudi et al., 2009; Koutsoudaki et al., 2009).”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Matsushima and Morell, 2001
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Strong astrogliosis comprising hypertrophy and hyperplasia of astrocytes occurs as a response to cuprizone treatment in different white and gray matter structures for instance the CC (Matsushima and Morell, 2001; Gudi et al., 2009), hippocampus, (Koutsoudaki et al., 2009; Norkute et al., 2009), cerebellum, cortex (Skripuletz et al., 2008), and basal ganglia (Pott et al., 2009).”
From Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned (2014) · cites this paper as Matsushima and Morell, 2001
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Astrogliosis is an additional pathological hallmark of CUP treatment (Matsushima & Morell, 2001).”
From Activated microglia drive demyelination via CSF1R signaling (2021) · cites this paper as Matsushima & Morell, 2001
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Streit, W. J., Walter, S. A., & Pennell, N. A. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00069-0 · Cited by 1,096
Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice
Hiremath, M. M., Saito, Y., Knapp, G. W., Ting, J. P.-Y., Suzuki, K., & Matsushima, G. K. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00168-4 · Cited by 412
Self-citation(1978) · PubMed · Cited by 297
Nishiyama, A., Lin, X., Giese, N. A., Heldin, C., & Stallcup, W. B. (1996) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19960201)43:3 · Cited by 244
Insulin-Like Growth Factor-1 Inhibits Mature Oligodendrocyte Apoptosis during Primary Demyelination
Mason, J. L., Ye, P., Suzuki, K., D'Ercole, A. J., & Matsushima, G. K. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-15-05703.2000 · Cited by 237
Self-citationKomoly, S., Hudson, L. D., Webster, H. D., & Bondy, C. A. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.5.1894 · Cited by 223
Blakemore, W. F. (1972) · Journal of Neurocytology · doi:10.1007/bf01102943 · Cited by 217
Gene Expression in Brain during Cuprizone-Induced Demyelination and Remyelination
Morell, P., Barrett, C. V., Mason, J. L., Toews, A. D., Hostettler, J. D., Knapp, G. W., & Matsushima, G. K. (1998) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1998.0715 · Cited by 213
Self-citationDemyelination of the superior cerebellar peduncle in the mouse induced by cuprizone
Blakemore, W. F. (1973) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(73)90118-4 · Cited by 207
Blakemore, W. F. (1973) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(73)90119-6 · Cited by 177
Research works printed but not linked: 2
- Jurevics HA, 2000, Lipid metabolism during remyelination in brain, J Neurochem, 74, S32
- Ludwin SK, 1980, Chronic demyelination inhibits remyelination in the central nervous system, Lab Invest, 43, 382
Cited by
Sorted by citations
Demyelination increases radial diffusivity in corpus callosum of mouse brain
Song, S.-K., Yoshino, J., Le, T. Q., Lin, S.-J., Sun, S.-W., Cross, A. H., & Armstrong, R. C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.01.028 · Cited by 1,658
Remyelination in the CNS: from biology to therapy
Franklin, R. J. M., & ffrench-Constant, C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2480 · Cited by 1,544
Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms
Alizadeh, A., Dyck, S. M., & Karimi‐Abdolrezaee, S. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00282 · Cited by 1,509
TNFα promotes proliferation of oligodendrocyte progenitors and remyelination
Arnett, H. A., Mason, J., Marino, M., Suzuki, K., Matsushima, G. K., & Ting, J. P.-Y. (2001) · Nature Neuroscience · doi:10.1038/nn738 · Cited by 1,012
Self-citationOligodendrocytes in development, myelin generation and beyond
Kuhn, S., Gritti, L., Crooks, D., & Dombrowski, Y. (2019) · Cells · doi:10.3390/cells8111424 · Cited by 625
Inefficient clearance of myelin debris by microglia impairs remyelinating processes
Lampron, A., Larochelle, A., Laflamme, N., Préfontaine, P., Plante, M.-M., Sánchez, M. G., Yong, V. W., Stys, P. K., Tremblay, M.-È., & Rivest, S. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20141656 · Cited by 595
Active induction of experimental allergic encephalomyelitis
Stromnes, I. M., & Goverman, J. M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.285 · Cited by 572
Activation of Necroptosis in Multiple Sclerosis
Ofengeim, D., Ito, Y., Najafov, A., Zhang, Y., Shan, B., DeWitt, J. P., Ye, J., Zhang, X., Chang, A., Vakifahmetoglu-Norberg, H., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.051 · Cited by 526
TREM2 sustains microglial expansion during aging and response to demyelination
Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S., & Colonna, M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77983 · Cited by 525
Multiple sclerosis: experimental models and reality
Lassmann, H., & Bradl, M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1631-4 · Cited by 525
A regenerative approach to the treatment of multiple sclerosis
Deshmukh, V. A., Tardif, V., Lyssiotis, C. A., Green, C. C., Kerman, B., Kim, H. J., Padmanabhan, K., Swoboda, J. G., Ahmad, I., Kondo, T., et al. (2013) · Nature · doi:10.1038/nature12647 · Cited by 531
Translocator protein 18 kDa (TSPO): Molecular sensor of brain injury and repair
Chen, M.-K., & Guilarte, T. R. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.12.004 · Cited by 506
Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology
Voet, S., Prinz, M., & van Loo, G. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.11.005 · Cited by 503
Shen, S., Sandoval, J., Swiss, V. A., Li, J., Dupree, J. L., Franklin, R. J. M., & Casaccia‐Bonnefil, P. (2008) · Nature Neuroscience · doi:10.1038/nn.2172 · Cited by 499
Understanding the Physiopathology Behind Axial and Radial Diffusivity Changes—What Do We Know?
Winklewski, P. J., Sabisz, A., Naumczyk, P., Jodzio, K., Szurowska, E., & Szarmach, A. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00092 · Cited by 463
Kirby, L., Jin, J., Cardona, J. G., Smith, M. D., Martin, K. A., Wang, J., Strasburger, H., Herbst, L., Alexis, M., Karnell, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11638-3 · Cited by 436
Praet, J., Guglielmetti, C., Berneman, Z., Van der Linden, A., & Ponsaerts, P. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.004 · Cited by 435
bHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS
Arnett, H. A., Fancy, S. P. J., Alberta, J. A., Zhao, C., Plant, S. R., Kaing, S., Raine, C. S., Rowitch, D. H., Franklin, R. J. M., & Stiles, C. D. (2004) · Science · doi:10.1126/science.1103709 · Cited by 416
NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes
Freeman, L., Guo, H., David, C. N., Brickey, W. J., Jha, S., & Ting, J. P.-Y. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20150237 · Cited by 397
Cignarella, F., Filipello, F., Bollman, B., Cantoni, C., Locca, A., Mikesell, R., Manis, M., Ibrahim, A., Deng, L., Benitez, B. A., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02193-z · Cited by 392
Quantification of increased cellularity during inflammatory demyelination
Wang, Y., Wang, Q., Haldar, J. P., Yeh, F.-C., Xie, M., Sun, P., Tu, T.-W., Trinkaus, K., Klein, R. S., Cross, A. H., et al. (2011) · Brain · doi:10.1093/brain/awr307 · Cited by 384
Animal models of multiple sclerosis: the good, the bad and the bottom line
Ransohoff, R. M. (2012) · Nature Neuroscience · doi:10.1038/nn.3168 · Cited by 379
Skripuletz, T., Hackstette, D., Bauer, K., Gudi, V., Pul, R., Voss, E., Berger, K., Kipp, M., Baumgärtner, W., & Stangel, M. (2013) · Brain · doi:10.1093/brain/aws262 · Cited by 376
Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned
Gudi, V., Gingele, S., Skripuletz, T., & Stangel, M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00073 · Cited by 375
“Demyelination peaks between 4.5 and 5 weeks of cuprizone exposure in the CC and between 5 and 6 weeks in the cortex and hippocampus (Hiremath et al., 1998; Matsushima and Morell, 2001; Skripuletz et al., 2008; Gudi et al., 2009; Koutsoudaki et al., 2009).”
BackgroundInfluentialAnimal models of Multiple Sclerosis
Procaccini, C., Rosa, V. D., Pucino, V., Formisano, L., & Matarese, G. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.03.042 · Cited by 403
Identification of a microglia phenotype supportive of remyelination
Olah, M., Amor, S., Brouwer, N., Vinet, J., Eggen, B., Biber, K., & Boddeke, H. W. G. M. (2012) · Glia · doi:10.1002/glia.21266 · Cited by 358
The cuprizone model for demyelination
Torkildsen, Ø., Brunborg, L. A., Myhr, K.-M., & Bø, L. (2008) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2008.01036.x · Cited by 346
Jha, S., Srivastava, S. Y., Brickey, W. J., Iocca, H., Toews, A., Morrison, J. P., Chen, V. S., Gris, D., Matsushima, G. K., & Ting, J. P.-Y. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4088-10.2010 · Cited by 310
Self-citationThe relevance of animal models in multiple sclerosis research
Đenić, A., Johnson, A. J., Bieber, A. J., Warrington, A. E., Rodriguez, M., & Pirko, I. (2010) · Pathophysiology · doi:10.1016/j.pathophys.2010.04.004 · Cited by 312
TREM2 regulates microglial cell activation in response to demyelination in vivo
Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C. M., Galimberti, D., Olivecrona, G., Klein, R. S., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1388-1 · Cited by 296
Remyelination therapies: a new direction and challenge in multiple sclerosis
Plemel, J. R., Liu, W., & Yong, V. W. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.115 · Cited by 293
Human Copper Transporters: Mechanism, Role in Human Diseases and Therapeutic Potential
Gupta, A., & Lutsenko, S. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.84 · Cited by 276
Xing, Y. L., Röth, P. T., Stratton, J. A. S., Chuang, B. H. A., Danne, J., Ellis, S. L., Ng, S. W., Kilpatrick, T. J., & Merson, T. D. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3491-13.2014 · Cited by 275
Remyelination in Experimental Models of Toxin-Induced Demyelination
Blakemore, W. F., & Franklin, R. J. M. (2008) · Current Topics in Microbiology and Immunology · doi:10.1007/978-3-540-73677-6_8 · Cited by 275
Cortical Demyelination Is Prominent in the Murine Cuprizone Model and Is Strain-Dependent
Skripuletz, T., Lindner, M., Kotsiari, A., Garde, N., Fokuhl, J., Linsmeier, F., Trebst, C., & Stangel, M. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.070850 · Cited by 271
Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation
Wheeler, M. A., Jaronen, M., Covacu, R., Zandee, S., Scalisi, G., Rothhammer, V., Tjon, E. C., Chao, C., Kenison, J. E., Blain, M., et al. (2019) · Cell · doi:10.1016/j.cell.2018.12.012 · Cited by 258
Regional differences between grey and white matter in cuprizone induced demyelination
Gudi, V., Moharregh-Khiabani, D., Skripuletz, T., Koutsoudaki, P. N., Kotsiari, A., Skuljec, J., Trebst, C., & Stangel, M. (2009) · Brain Research · doi:10.1016/j.brainres.2009.06.005 · Cited by 252
Cells of the oligodendroglial lineage, myelination, and remyelination
Miron, V. E., Kuhlmann, T., & Antel, J. P. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.09.010 · Cited by 249
Microglial Recruitment, Activation, and Proliferation in Response to Primary Demyelination
Remington, L. T., Babcock, A. A., Zehntner, S. P., & Owens, T. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060783 · Cited by 234
Zirngibl, M., Assinck, P., Sizov, A., Caprariello, A. V., & Plemel, J. R. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00538-8 · Cited by 233
Schregel, K., Tysiak, E., Garteiser, P., Gemeinhardt, I., Prozorovski, T., Aktaş, O., Merz, H., Petersen, D., Wuerfel, J. T., & Sinkus, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200151109 · Cited by 228
Extensive remyelination of the CNS leads to functional recovery
Duncan, I. D., Brower, A., Kondo, Y., Curlee, J. F., & Schultz, R. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812500106 · Cited by 227
Disease-associated oligodendrocyte responses across neurodegenerative diseases
Pandey, S., Shen, K., Lee, S.-H., Shen, Y.-A. A., Wang, Y., Otero-García, M., Kotova, N., Vito, S. T., Laufer, B. I., Newton, D. F., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111189 · Cited by 227
Quantifying the early stages of remyelination following cuprizone-induced demyelination
Stidworthy, M. F., Genoud, S., Suter, U., Mantei, N., & Franklin, R. J. M. (2003) · Brain Pathology · doi:10.1111/j.1750-3639.2003.tb00032.x · Cited by 224
Lin, W., Kemper, A., Dupree, J. L., Harding, H. P., Ron, D., & Popko, B. (2006) · Brain · doi:10.1093/brain/awl044 · Cited by 222
Progesterone Synthesis in the Nervous System: Implications for Myelination and Myelin Repair
Schumacher, M., Hussain, R., Gago, N., Oudinet, J., Mattern, C., & Ghoumari, A. M. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00010 · Cited by 233
The benefits and detriments of macrophages/microglia in models of multiple sclerosis
Rawji, K. S., & Yong, V. W. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/948976 · Cited by 217
Liu, L., Belkadi, A., Darnall, L., Hu, T., Drescher, C., Cotleur, A. C., Padovani-Claudio, D., He, T., Choi, K., Lane, T. E., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2491 · Cited by 214
Lee, J., Shmueli, K., Kang, B., Yao, B., Fukunaga, M., van Gelderen, P., Palumbo, S., Bosetti, F., Silva, A. C., & Duyn, J. H. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.10.076 · Cited by 212
Voß, E. V., Škuljec, J., Gudi, V., Skripuletz, T., Pul, R., Trebst, C., & Stangel, M. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.09.008 · Cited by 202
Environmental risk factors for multiple sclerosis
Salzer, J. (2013) · KTH Publication Database DiVA (KTH Royal Institute of Technology) · Cited by 202
Nations, S., Boyer, P. J., Love, L. A., Burritt, M. F., Butz, J. A., Wolfe, G. I., Hynan, L. S., Reisch, J., & Trivedi, J. R. (2008) · Neurology · doi:10.1212/01.wnl.0000312375.79881.94 · Cited by 201
AMPK activation: Role in the signaling pathways of neuroinflammation and neurodegeneration
Peixoto, C. A., Oliveira, W. H. D., Araújo, S. M. D. R., & Nunes, A. K. S. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.08.013 · Cited by 196
Vitamin K and the Nervous System: An Overview of its Actions
Ferland, G. (2012) · Advances in Nutrition · doi:10.3945/an.111.001784 · Cited by 202
Behavioral deficits in the cuprizone-induced murine model of demyelination/remyelination
Franco-Pons, N., Torrente, M., Colomina, M. T., & Vilella, E. (2007) · Toxicology Letters · doi:10.1016/j.toxlet.2007.01.010 · Cited by 195
Ács, P., Kipp, M., Norkutė, A., Johann, S., Clarner, T., Braun, A., Berente, Z., Komoly, S., & Beyer, C. (2008) · Glia · doi:10.1002/glia.20806 · Cited by 194
Mechanisms of white matter damage in multiple sclerosis
Lassmann, H. (2014) · Glia · doi:10.1002/glia.22597 · Cited by 191
Xiao, L., Xu, H., Zhang, Y., Wei, Z., He, J., Jiang, W., Li, X., Dyck, L. E., Devon, R. M., Deng, Y., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002064 · Cited by 191
Arnett, H. A., Wang, Y., Matsushima, G. K., Suzuki, K., & Ting, J. P.-Y. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-30-09824.2003 · Cited by 190
Self-citationJelescu, I. O., Zurek, M., Winters, K. V., Veraart, J., Rajaratnam, A., Kim, N. S., Babb, J. S., Shepherd, T. M., Novikov, D. S., Kim, S. G., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.02.004 · Cited by 188
Five Decades of Cuprizone, an Updated Model to Replicate Demyelinating Diseases
Vega-Riquer, J. M., Mendez-Victoriano, G., Morales-Luckie, R. A., & Gonzalez-Perez, O. (2019) · Current Neuropharmacology · doi:10.2174/1570159x15666170717120343 · Cited by 188
Steelman, A. J., Thompson, J. P., & Li, J. (2012) · Neuroscience Research · doi:10.1016/j.neures.2011.10.002 · Cited by 183
Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis
Bjelobaba, I. M., Begović-Kuprešanin, V., Peković, S., & Lavrnja, I. C. (2018) · Journal of Neuroscience Research · doi:10.1002/jnr.24224 · Cited by 197
Oligodendrogenesis in the normal and pathological central nervous system
Waly, B. E., Macchi, M., Cayre, M., & Durbec, P. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00145 · Cited by 193
Armstrong, R. C., Le, T. Q., Frost, E. E., Borke, R. C., & Vana, A. C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-19-08574.2002 · Cited by 178
Mason, J. L., Xuan, S., Dragatsis, I., Efstratiadis, A., & Goldman, J. E. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07710.2003 · Cited by 177
The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination
Hussain, R., Ghoumari, A. M., Bielecki, B., Steibel, J., Boehm, N., Lière, P., Macklin, W. B., Kumar, N., Habert, R., Mhaouty‐Kodja, S., et al. (2013) · Brain · doi:10.1093/brain/aws284 · Cited by 189
Pasquini, L. A., Calatayud, C. A., Bertone Uña, A. L., Millet, V., Pasquini, J. M., & Soto, E. F. (2007) · Neurochemical Research · doi:10.1007/s11064-006-9165-0 · Cited by 176
Xie, M., Tobin, J. E., Budde, M. D., Chen, C.-I., Trinkaus, K., Cross, A. H., McDaniel, D. P., Song, S.-K., & Armstrong, R. C. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181e3de90 · Cited by 175
Harsan, L. A., Steibel, J., Zaremba, A., Agin, A., Sapin, R., Poulet, P., Guignard, B., Parizel, N., Grucker, D., Boehm, N., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4453-08.2008 · Cited by 177
Neurodegeneration in multiple sclerosis
Mey, G. M., Mahajan, K. R., & DeSilva, T. M. (2022) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1583 · Cited by 188
Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination
Samanta, J., Grund, E. M., Silva, H. M., Lafaille, J. J., Fishell, G., & Salzer, J. L. (2015) · Nature · doi:10.1038/nature14957 · Cited by 170
Ji, B., Maeda, J., Sawada, M., Ono, M., Okauchi, T., Inaji, M., Zhang, M.-R., Suzuki, K., Ando, K., Staufenbiel, M., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2312-08.2008 · Cited by 169
Lindner, M., Heine, S., Haastert, K., Garde, N., Fokuhl, J., Linsmeier, F., Grothe, C., Baumgärtner, W., & Stangel, M. (2008) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00879.x · Cited by 169
Microglia plasticity during health and disease: An immunological perspective
Shemer, A., Erny, D., Jung, S., & Prinz, M. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.003 · Cited by 168
The T3-induced gene KLF9 regulates oligodendrocyte differentiation and myelin regeneration
Dugas, J. C., Ibrahim, A., & Barres, B. A. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.03.007 · Cited by 167
Reduced astrocytic NF-κB activation by laquinimod protects from cuprizone-induced demyelination
Brück, W., Pförtner, R., Pham, T., Zhang, J., Hayardeny, L., Piryatinsky, V., Hanisch, U., Regen, T., van Rossum, D., Brakelmann, L., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1009-1 · Cited by 170
LIEBETANZ, D., & MERKLER, D. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.05.032 · Cited by 166
Functional roles of transferrin in the brain
Leitner, D., & Connor, J. R. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.10.016 · Cited by 173
Guglielmetti, C., Veraart, J., Roelant, E., Mai, Z., Daans, J., Audekerke, J. V., Naeyaert, M., Vanhoutte, G., y Palacios, R. D., Praet, J., et al. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.10.052 · Cited by 160
McMahon, E. J., Suzuki, K., & Matsushima, G. K. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00205-9 · Cited by 161
Self-citationChari, D. M., & Blakemore, W. F. (2002) · Glia · doi:10.1002/glia.10038 · Cited by 163
Deloulme, J., Raponi, É., Gentil, B. J., Bertacchi, N., Marks, A., Labourdette, G., & Baudier, J. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.07.008 · Cited by 163
Promoting remyelination in multiple sclerosis
Cunniffe, N. G., & Coles, A. J. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09421-x · Cited by 172
Stidworthy, M. F. (2004) · Brain · doi:10.1093/brain/awh217 · Cited by 164
Murtie, J. C., Zhou, Y.-X., Le, T. Q., Vana, A. C., & Armstrong, R. C. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.12.006 · Cited by 157
Selvaraju, R., Bernasconi, L., Losberger, C., Graber, P., Kadi, L., Avellana-Adalid, V., Picard-Riera, N., Van Evercooren, A. B., Cirillo, R., Kosco-Vilbois, M., et al. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2003.12.014 · Cited by 156
Clarner, T., Diederichs, F., Berger, K., Denecke, B., Gan, L., van der Valk, P., Beyer, C., Amor, S., & Kipp, M. (2012) · Glia · doi:10.1002/glia.22367 · Cited by 155
Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair
Siebert, J. R., Conta, A. C., & Osterhout, D. J. (2014) · BioMed Research International · doi:10.1155/2014/845323 · Cited by 159
Dietary cholesterol promotes repair of demyelinated lesions in the adult brain
Berghoff, S. A., Gerndt, N., Winchenbach, J., Stumpf, S. K., Hosang, L., Odoardi, F., Ruhwedel, T., Böhler, C., Barrette, B., Stassart, R., et al. (2017) · Nature Communications · doi:10.1038/ncomms14241 · Cited by 151
Aryanpour, R., Pasbakhsh, P., Zibara, K., Namjoo, Z., Boroujeni, F. B., Shahbeigi, S., Kashani, I. R., Beyer, C., & Zendedel, A. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.08.007 · Cited by 156
Cuprizone [Bis(Cyclohexylidenehydrazide)] is Selectively Toxic for Mature Oligodendrocytes
Bénardais, K., Kotsiari, A., Škuljec, J., Koutsoudaki, P. N., Gudi, V., Singh, V., Vulinović, F., Skripuletz, T., & Stangel, M. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9380-9 · Cited by 148
Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination
Thiessen, J. D., Zhang, Y., Zhang, H., Wang, L., Buist, R., Del Bigio, M. R., Kong, J., Li, X., & Martin, M. (2013) · NMR in Biomedicine · doi:10.1002/nbm.2992 · Cited by 148
Konradi, C. L., Daws, S. E., & Clay, H. B. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.025 · Cited by 148
Activated microglia drive demyelination via CSF1R signaling
Marzan, D. E., Brügger‐Verdon, V., West, B. L., Liddelow, S., Samanta, J., & Salzer, J. L. (2021) · Glia · doi:10.1002/glia.23980 · Cited by 147
“Upon removal of CUP from the diet, there is robust remyelination (Matsushima & Morell, 2001; Praet, Guglielmetti, Berneman, Van der Linden, & Ponsaerts, 2014; Wergeland, Torkildsen, Myhr, Mørk, & Bø, 2012).”
BackgroundInfluentialFranco, P. G., Silvestroff, L., Soto, E. F., & Pasquini, J. M. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.04.039 · Cited by 147
Levels of BDNF Impact Oligodendrocyte Lineage Cells following a Cuprizone Lesion
VonDran, M. W., Singh, H., Honeywell, J. Z., & Dreyfus, C. F. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6595-10.2011 · Cited by 144
Inherited and acquired disorders of myelin: The underlying myelin pathology
Duncan, I. D., & Radcliff, A. B. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.04.002 · Cited by 146
Statin Therapy Inhibits Remyelination in the Central Nervous System
Miron, V. E., Zehntner, S. P., Kuhlmann, T., Ludwin, S. K., Owens, T., Kennedy, T. E., Bedell, B. J., & Antel, J. P. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080947 · Cited by 141
Li, C., Xiao, L., Liu, X., Yang, W., Shen, W., Hu, C., Yang, G., & He, C. (2013) · Glia · doi:10.1002/glia.22469 · Cited by 144
Metadata
- Authors
- Matsushima, G. K., & Morell, P.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Matsushima, Glenn K.
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2001-01
- Volume
- 11
- Issue
- 1
- Pages
- 107-116
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8098267
- OpenAlex
- W2100904149
- Cited by
- 984
- References
- 45
- Citations by year
- 2026: 31 · 2025: 38 · 2024: 42 · 2023: 50 · 2022: 58 · 2021: 48 · 2020: 55 · 2019: 75 · 2018: 59 · 2017: 65 · 2016: 39 · 2015: 58 · 2014: 39 · 2013: 53 · 2012: 40
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns011615-29, 5r01ns037815-05, 5r29ns035372-05)
- National Institute of Neurological Disorders and Stroke (NS37815, NS-11615, NS-35372)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cuprizone, demyelination, remyelination, oligodendrocyte apoptosis, microglia, myelin phagocytosis, oligodendrocyte precursor cells, myelin gene expression, C57BL/6 mice, copper chelators
- MeSH terms
- Animals, Central Nervous System, Chelating Agents, Cuprizone, Demyelinating Diseases, Mice, Inbred C57BL, Myelin Sheath, Oligodendroglia, Microglia, Models, Animal, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
