Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned

In the paper

“However, oligodendrocyte death was not prevented in mice lacking FAS in oligodendrocytes revealing that FAS is also not essential for the induction of apoptosis in the cuprizone model (Hesse et al., 2010).”

What the sources say

• Supported

  The Discussion reports no difference in the number of apoptotic cells or in oligodendroglial cell death when FAS was absent in the cuprizone model. It concludes that FAS is not necessary for this cell death, supporting the citing sentence. Page numbers are not provided in our copy. (LLM, conf=0.92)

  cites Hesse et al., 2010 source

In the paper

“Additionally, despite of a similar extent of astro- and microgliosis as well as OPC response in both genders, female SJL mice were partially resistant to the demyelination in the CC.”

What the sources say

• Partly supported

  The Discussion (page unavailable) reports that female SJL mice had less severe demyelination than males, citing an earlier study. The passages on astrocytes and microglia (pages unavailable) find similar responses between sexes in C57BL/6 mice, not SJL mice; our copy does not establish a similar OPC response in SJL mice. (LLM, conf=0.87)

  cites Taylor et al., 2010 sourceExperimental — accuracy not yet measured

In the paper

“During cuprizone-induced demyelination, oligodendrocytes start to undergo apoptosis after 3–7 days of cuprizone exposure (Mason et al., 2000a; Komoly, 2005; Hesse et al., 2010).”

What the sources say

• ?Not checked — no full text of the sourcecites Mason et al., 2000a source
• ?Not checked — no full text of the sourcecites Komoly, 2005
• Partly supported

  The Results section reports apoptotic oligodendrocytes on day 6, within the claimed 3–7-day window. But it also reports apoptotic oligodendrocytes 2 days after the diet began, so the paper does not support 3–7 days as the time apoptosis starts. (LLM, conf=0.87)

  cites Hesse et al., 2010 sourceExperimental — accuracy not yet measured

In the paper

“Once demyelination is complete the amount of activated RCA-1 (RCA, Ricinus communis agglutinin-1)/Mac-3-positive microglia starts to decrease (Mason et al., 2004; Skripuletz et al., 2011b).”

What the sources say

• Partly supported

  In “The Presence of Microglia/Macrophages Coincides with Demyelination and Oligodendrocyte Death” (page not available), RCA-1-positive microglia/macrophages decline after mice return to a normal diet. But their numbers remain elevated in chronically demyelinated mice kept on cuprizone, so completion of demyelination alone does not establish the claimed decline. The paper identifies these cells with RCA-1, not Mac-3. (LLM, conf=0.87)

  cites Mason et al., 2004 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Skripuletz et al., 2011b source

In the paper

“The up-regulation of MHC-II at the peak of demyelination may be of relevance for the induction of remyelination since MHC-II −/− mice showed delayed remyelination and regeneration of oligodendrocytes after cuprizone-induced demyelination (Arnett et al., 2003).”

What the sources say

• Supported

  The section “Expression of MHC-I and -II during demyelination and remyelination” reports that MHC-II transcription peaks during cuprizone treatment. “Roles of MHC-I and -II in remyelination” reports delayed remyelination and fewer regenerating oligodendrocytes in MHC-II-null mice, supporting the claim’s hedged interpretation. Page numbers were not available for these passages. (LLM, conf=0.91)

  cites Arnett et al., 2003 source

In the paper

“MHC-II −/− mice showed delayed remyelination and regeneration of oligodendrocytes after cuprizone-induced demyelination (Arnett et al., 2003).”

What the sources say

• Supported

  In “Roles of MHC-I and -II in remyelination” (page not specified in the excerpts), the paper reports a significant delay in remyelination in MHC-II-null mice after cuprizone treatment. The same section reports fewer regenerated oligodendrocytes than in wild-type mice after one week of recovery. (LLM, conf=0.94)

  cites Arnett et al., 2003 source

In the paper

“Upon chronic cuprizone administration (12–16 weeks) newly generated oligodendrocytes progressively undergo apoptosis.”

What the sources say

• Partly supported

  The section “The Mature Oligodendrocyte Population Is Inadequately Regenerated within Chronically Demyelinated Lesion” reports apoptotic oligodendrocytes during prolonged cuprizone feeding, and Figure 2 quantifies them through 12 weeks. Although “Induction of Acute and Chronic Demyelination” says mice were fed cuprizone for up to 16 weeks, the cited passages do not establish that newly generated oligodendrocytes progressively underwent apoptosis throughout the stated 12–16-week period. Page numbers are unavailable in our copy. (LLM, conf=0.84)

  cites Mason et al., 2004 sourceExperimental — accuracy not yet measured

In the paper

“After 3 weeks of cuprizone treatment mature oligodendrocytes are almost completely depleted (Hesse et al., 2010; Skripuletz et al., 2011b).”

What the sources say

• Supported

  The Results section reports 17 ± 15 Nogo-A-positive mature oligodendrocytes per mm² after 21 days of cuprizone treatment, compared with 1797 ± 404 in untreated controls. The Discussion states that the vast majority of mature oligodendrocytes undergo cell death during the first three weeks. Page numbers were not provided in our copy. (LLM, conf=0.94)

  cites Hesse et al., 2010 source
• ?Not checked — no full text of the sourcecites Skripuletz et al., 2011b source

In the paper

“Furthermore, also the pool of OPC becomes diminished (Mason et al., 2004).”

What the sources say

• Supported

  The paper’s opening summary (p. 1673) states that oligodendrocyte progenitors become progressively depleted within lesions when mice remain on a cuprizone diet. The Figure 2 caption also describes progressive depletion of the progenitor population during continuous cuprizone exposure. (LLM, conf=0.94)

  cites Mason et al., 2004 source

In the paper

“Similar associations are also observed in post-mortem tissue from MS patients and in EAE challenged animals (Prineas and Connell, 1979; Nishiyama et al., 1997; Wolswijk, 2002; Patani et al., 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Prineas and Connell, 1979 source
• ?Not checked — no full text of the sourcecites Nishiyama et al., 1997 source
• Partly supported

  In the section on factors influencing OPC density (page not available), Wolswijk reports a positive correlation between OPC and macrophage densities in lesions from people with chronic MS. The tissue-characteristics section also identifies activated microglia/macrophages in the samples. The paper does not report the claimed association in EAE-challenged animals, so it supports only the post-mortem MS-tissue portion of the sentence. (LLM, conf=0.85)

  cites Wolswijk, 2002 sourceExperimental — accuracy not yet measured

In the paper

“Nevertheless, demyelinated axons retain the ability to be remyelinated as shown by transplantation of OPC into the lesions (Mason et al., 2004).”

What the sources say

• Supported

  In the Results section, the authors transplanted O4+ progenitors into chronically demyelinated corpus callosum lesions to test whether the axons could be remyelinated. They report substantially more myelinated axons in transplanted mice than in controls, supporting the claim in the cuprizone mouse model. (LLM, conf=0.94)

  cites Mason et al., 2004 source

In the paper

“In contrast, activated microglia persist at a low level in chronically demyelinated lesions in mice treated with cuprizone up to 12 weeks (Mason et al., 2004; Lindner et al., 2009).”

What the sources say

• Partly supported

  The Figure 4 caption reports a few RCA-1-positive microglia/macrophages in the chronically demyelinated corpus callosum after 12 weeks of cuprizone feeding. The section on microglia/macrophages says their numbers remained elevated relative to controls. The paper supports persistence at a low level, but these passages do not establish that the cells were specifically activated microglia rather than microglia/macrophages. (LLM, conf=0.84)

  cites Mason et al., 2004 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Lindner et al., 2009 source

In the paper

“Indeed, in response to cuprizone a very small number of T cells was recruited to the demyelinated CC and these T cells did not display an activated phenotype (Remington et al., 2007).”

What the sources say

• Supported

  The section “T Cells Are Recruited to the Demyelinated Corpus Callosum” reports that T-cell numbers rose during cuprizone treatment, reaching 1,630 ± 290 after six weeks—a small number relative to the corpus callosum’s total cell count reported in the cellularity section. It also reports that the T-cell activation markers CD44 and CD69 were not up-regulated. Page numbers were not available in our copy. (LLM, conf=0.92)

  cites Remington et al., 2007 source

In the paper

“Overall, cuprizone-induced de- and remyelination are not mediated by B or T cells, as shown by the use of RAG −/− mice that lack lymphocytes (Arnett et al., 2001; Hiremath et al., 2008).”

What the sources say

• ?Not checked — no full text of the sourcecites Arnett et al., 2001 source
• Partly supported

  The Results section (‘T cells are not required for activating MHC II’; page unavailable) reports that cuprizone-treated RAG-1−/− mice, which lack B and T cells, had demyelination similar to wild-type mice. The Discussion says T cells do not play a role in remyelination, citing Arnett et al. (2001), but this paper does not report a RAG-1−/− remyelination comparison or establish the same conclusion for B cells during remyelination. (LLM, conf=0.85)

  cites Hiremath et al., 2008 sourceExperimental — accuracy not yet measured

In the 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).”

What the sources say

• ?Could not verify

  The available summary describes cuprizone-induced demyelination, microglial recruitment, and remyelination, but does not describe astrogliosis in the corpus callosum. Searches for astrocyte hypertrophy, hyperplasia, astrogliosis, and corpus callosum found no passage establishing the response attributed to Matsushima and Morell; the other named regions have separate citations in the citing sentence. (LLM, conf=0.70)

  cites Matsushima and Morell, 2001 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Gudi et al., 2009 source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Skripuletz et al., 2008 sourceExperimental — accuracy not yet measured

In the paper

“In contrast, a subset of peripheral macrophages (CD11b+/CD45high) infiltrated into the demyelinated CC of cuprizone-treated mice (McMahon et al., 2002; Remington et al., 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites McMahon et al., 2002 source
• Supported

  The “Macrophage/Microglial Response in the Demyelinated Corpus Callosum” section identifies CD11b-positive, CD45-high cells as infiltrating blood-derived macrophages. It reports that their number rose significantly in the demyelinated corpus callosum of cuprizone-treated mice, while they remained a small fraction of CD11b-positive cells. (LLM, conf=0.94)

  cites Remington et al., 2007 source

In the paper

“these T cells did not display an activated phenotype (Remington et al., 2007)”

What the sources say

• Supported

  The Discussion states that T cells infiltrating the demyelinated corpus callosum did not show an activated phenotype. The section ‘T Cells Are Recruited to the Demyelinated Corpus Callosum’ also reports that the activation markers CD44 and CD69 were not up-regulated on those T cells. (LLM, conf=0.95)

  cites Remington et al., 2007 source

In the paper

“Remington and co-workers reported that only 0.5% of the CD11b+ population is CD45high and thus represents infiltrating macrophages.”

What the sources say

• Partly supported

  The Macrophage/Microglial Response section reports that, at 4.5 weeks of cuprizone treatment, CD45-dim microglia comprised 99.5% of CD11b-positive cells in the corpus callosum; it identifies CD45-high cells as blood-derived macrophages. The remaining approximately 0.5% supports the figure, but the citing sentence omits the treatment and time point that bound it. (LLM, conf=0.85)

  cites Remington et al., 2007 sourceExperimental — accuracy not yet measured

In the paper

“In addition, in this model microglia seem not to be assigned to a certain phenotype characteristic either for de- or remyelination since most of the genes that were regulated showed an unidirectional up-regulation or down-regulation throughout the de- and remyelination processes (Olah et al., 2012)”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Olah et al., 2012 source

In the paper

“however, in chronic cuprizone lesions there are no signs of astroglial scar properties (Hibbits et al., 2012).”

What the sources say

• Partly supported

  The Discussion says cuprizone lesions lacked an astroglial scar interface with fibrillar collagen, and the Results report no collagen fibrils in chronic lesions. But the Results also report increased scar-associated extracellular matrix molecules, while the Discussion describes a dense network of GFAP- and Vim-expressing astrocyte processes in chronic lesions. Thus, the paper supports the absence of a fibrotic scar, not the absence of all astroglial scar properties. (LLM, conf=0.88)

  cites Hibbits et al., 2012 sourceExperimental — accuracy not yet measured

In the paper

“Olah and colleges have shown that CD247 (B7-H1), a known immune inhibitory molecule (Magnus et al., 2005; Ortler et al., 2008) was up-regulated on microglia throughout de- and remyelination (Olah et al., 2012).”

What the sources say

• Supported

  The Discussion states that Cd247 (B7-H1) was strongly regulated during demyelination and remyelination: its expression was induced at 2WD and remained upregulated during remyelination. The Microglia Phenotype section labels the upregulated gene Cd274, an inconsistency in the paper's naming, but the Discussion directly supports the attributed wording. (LLM, conf=0.90)

  cites Olah et al., 2012 source

In the paper

“while Axl and Mer were found on activated microglia (Binder et al., 2008)”

What the sources say

• Supported

  In the section on Gas6 and its receptors during demyelination, double-label staining showed that the vast majority of Axl- and Mer-positive cells also expressed the microglial marker IBA1 during cuprizone challenge. The section on microglial activation also reports increased Axl and Mer gene expression in LPS-activated microglia. (LLM, conf=0.94)

  cites Binder et al., 2008 source

In the paper

“In untreated mice Tyro3 co-localizes with CNPase.”

What the sources say

• Supported

  The section “Gas6 and its receptors are regulated in a mouse model of demyelination” reports that, in healthy mice, some Tyro3-expressing cells in the corpus callosum colocalize with CNPase. The Discussion likewise states that CNPase-positive oligodendrocytes in the healthy mouse corpus callosum express Tyro3. (LLM, conf=0.94)

  cites Binder et al., 2008 source

In the paper

“Additionally, IL-1β did not display any impact on depletion of oligodendrocytes following cuprizone treatment (Mason et al., 2001).”

What the sources say

• Supported

  The Discussion states that mature oligodendrocyte depletion during demyelination progressed similarly in IL-1β-deficient and wild-type mice. The results section likewise reports depletion in both groups after five weeks of cuprizone exposure. This concerns depletion, not the later regeneration of oligodendrocytes, which the paper says was impaired without IL-1β. (LLM, conf=0.94)

  cites Mason et al., 2001 source

In the paper

“Surprisingly, remyelination was enhanced when LtβR-signaling was inhibited by an LtβR-Ig fusion decoy protein.”

What the sources say

• Supported

  The “Inhibition of LtβR enhances remyelination” section reports significantly greater remyelination in cuprizone-treated mice given inhibitory LtβR-mIg than in mice given control Ig (Fig. 6; page not provided). This directly supports the claim in the studied mouse model. (LLM, conf=0.95)

  cites Plant et al., 2007 source

In the paper

“In the cuprizone model IL-1β was gradually up-regulated from the first week of cuprizone intoxication, then strongly increased at week 3 and sustained on this level until week 6 (Mason et al., 2001).”

What the sources say

• Partly supported

  The section “Expression of IL-1β precedes an increase in IGF-1 expression” reports a dramatic increase in IL-1β mRNA at week 3 that was sustained through week 6. It does not specify that up-regulation began in the first week or increased gradually before week 3. (LLM, conf=0.85)

  cites Mason et al., 2001 sourceExperimental — accuracy not yet measured

In the paper

“again emphasizing a beneficial role of the inflammatory response in the repair processes after a demyelinating insult.”

What the sources say

• Supported

  The Discussion states that inflammation may aid repair after demyelination. The paper also reports that MHC-II deficiency delayed remyelination and oligodendrocyte regeneration, supporting a beneficial role for parts of the inflammatory response; it cautions that not all immune-related molecules are beneficial. (LLM, conf=0.90)

  cites Arnett et al., 2003 source

In the paper

“In this study Mason and colleagues have shown that differentiation of OPC and thus, remyelination are dramatically reduced in absence of IL-1β”

What the sources say

• Supported

  In “NG2+ oligodendrocyte progenitor accumulation occurs in the absence of IL-1β,” the authors report that progenitors appear unable to mature in IL-1β-deficient mice. “Remyelination is dramatically reduced in the absence of IL-1β” reports significantly fewer remyelinated axons in those mice than in wild-type mice. (LLM, conf=0.92)

  cites Mason et al., 2001 source

In the paper

“However, remyelination was slightly delayed in mice lacking LtβR (Plant et al., 2007).”

What the sources say

• Supported

  The “Delayed remyelination in LtβR−/− mice” section reports modest but significant differences from wild-type mice at 7 and 10 weeks and concludes that remyelination was transiently delayed. By 12 weeks, the knockout mice had remyelinated to the same extent as controls. (LLM, conf=0.94)

  cites Plant et al., 2007 source

In the paper

“while LtβR by microglia (Plant et al., 2007).”

What the sources say

• Supported

  The Discussion states that microglia are a major source of LtβR expression during cuprizone treatment. The localization evidence concerns LtβR transcripts in regions enriched for microglia/macrophages; the paper also notes expression in astroglial-enriched regions. (LLM, conf=0.91)

  cites Plant et al., 2007 source

In the paper

“In particular, several genes of the MHC-family were reduced in the mice lacking TNF-α (Arnett et al., 2003).”

What the sources say

• Supported

  The section “Transcripts altered in mice lacking TNFα” explicitly states that several MHC-family genes were reduced in mice lacking TNFα. The comparison is with wild-type mice after demyelination and during remyelination; it does not describe a reduction before cuprizone treatment. (LLM, conf=0.95)

  cites Arnett et al., 2003 source

In the paper

“Moreover, these surviving oligodendrocytes even seem to retain the ability to remyelinate timely on week 5, regardless of remaining myelin debris (Mason et al., 2000b).”

What the sources say

• Partly supported

  The Discussion (page unavailable) says that remyelination occurred at weeks 4 and 5 in IGF-1 transgenic mice and that surviving mature oligodendrocytes most likely contributed. The Early recovery section (page unavailable) reports substantial remyelination at week 5. Our copy does not establish that myelin debris remained or that remyelination occurred regardless of it. (LLM, conf=0.86)

  cites Mason et al., 2000b sourceExperimental — accuracy not yet measured

In the paper

“suggesting a highly protective role of IGF-1 on oligodendrocytes.”

What the sources say

• Supported

  The ‘Survival of mature oligodendrocytes during demyelination’ section reports only a slight reduction in mature oligodendrocytes in IGF-1 transgenic mice, compared with a loss of more than 50% in wild-type mice after three weeks of cuprizone exposure. The Discussion says IGF-1 enhanced their survival and appeared to inhibit apoptotic death, supporting the citing sentence’s suggested protective role in this setting. (LLM, conf=0.92)

  cites Mason et al., 2000b source

In the paper

“Furthermore, instead of being nearly completely depleted, mature oligodendrocytes were numerously present in the CC of IGF-1 over-expressing mice during demyelination”

What the sources say

• Supported

  The Results section, “Survival of mature oligodendrocytes during demyelination,” reports severe depletion of mature oligodendrocytes in wild-type mice by week 5, but only a slight reduction in IGF-1 transgenic mice, with numbers returning to control levels by weeks 4–5. This supports the claimed contrast in the corpus callosum. (LLM, conf=0.94)

  cites Mason et al., 2000b source

In the paper

“In conditional mouse mutants, in which the expression of the Igf1r gene was ablated exclusively in neurons and OPC of the cerebrum, there was a reduced accumulation of OPC, leading to a decreased amount of newly generated oligodendrocytes (Mason et al., 2003).”

What the sources say

• Partly supported

  The sections on progenitor accumulation and mature oligodendrocyte regeneration report fewer progenitors and fewer regenerated oligodendrocytes in conditional mutants after cuprizone-induced demyelination. But the paper describes their spatial relationship as a correlation, not proof that reduced progenitor accumulation caused the decrease. The ablation section also reports low-level recombination in the cerebellum and testis, so deletion was not exclusively confined to neurons and OPCs of the cerebrum. (LLM, conf=0.86)

  cites Mason et al., 2003 sourceExperimental — accuracy not yet measured

In the paper

“A recent study of Zhou and colleagues showed that all four FGF receptors are highly regulated upon cuprizone treatment and during remyelination (Zhou et al., 2012).”

What the sources say

• Partly supported

  The Results section on FGF-family expression (page not provided) examines the cuprizone demyelination and recovery time course and identifies FGFR1 in a cluster of genes that increase during demyelination. It does not report that all four FGF receptors are highly regulated during treatment and remyelination; the Discussion's reference to multiple upregulated FGF-family members concerns ligands, not receptors. (LLM, conf=0.84)

  cites Zhou et al., 2012 sourceExperimental — accuracy not yet measured

In the paper

“We found that several growth factors such as FGF-2, CNTF, IGF-1, and glial cell-derived neurotrophic factor (GDNF) are strongly regulated during cuprizone treatment and/or in the recovery phase.”

What the sources say

• Supported

  The Results section reports changes in CNTF, IGF-1, and GDNF mRNA during cuprizone treatment or remyelination. Its growth-factor expression analysis also reports strongly regulated FGF-2 mRNA across the experimental period. The supplied passages do not specify page numbers. (LLM, conf=0.93)

  cites Gudi et al., 2011 source

In the paper

“Taking advantage of FGF-2 −/− mice Armstrong et al. have shown that the absence of FGF-2 leads to a faster regeneration/differentiation of oligodendrocytes after cuprizone-induced demyelination (Armstrong et al., 2002).”

What the sources say

• Supported

  The section on oligodendrocyte repopulation reports greater recovery in FGF2-null than wild-type mice after cuprizone treatment, with 87% more oligodendrocytes at the three-week recovery point. The paper also reports that reducing FGF2 promoted progenitor differentiation in culture, consistent with its findings in the knockout mice. Page numbers were not available in our copy. (LLM, conf=0.90)

  cites Armstrong et al., 2002 source

In the paper

“In contrast, in IFN-γR −/− mice cuprizone-induced microglia accumulation was initially diminished or simply delayed (Mana et al., 2006)”

What the sources say

• Supported

  The section “IFNγR−/− Mice Have Delayed Macrophages/Microglia Infiltration during Cuprizone Treatment” reports minimal microglial activation in knockout mice until week 4, while wild-type mice showed accumulation from week 2. It also reports no difference in microglial numbers between the groups from week 4 onward, supporting an initially diminished or delayed response. (LLM, conf=0.94)

  cites Mana et al., 2006 source

In the paper

“microgliosis was more pronounced in mice that constantly over-expressed IGF-1 within the brain after 3 weeks of cuprizone diet (Mason et al., 2000b).”

What the sources say

• Supported

  The section “Microglia/macrophage accumulation corresponds to demyelination” reports more microglia/macrophages in IGF-1 transgenic mice than in wild-type mice after three weeks of cuprizone feeding. “Elevated expression of IGF-1 in transgenic mice” confirms higher forebrain IGF-1 levels in the transgenic mice. Page numbers are not provided in our copy. (LLM, conf=0.94)

  cites Mason et al., 2000b source

In the paper

“Similar in the cuprizone model, a depletion of iNOS exacerbated demyelination (Arnett et al., 2002)”

What the sources say

• Supported

  The cuprizone-treatment results report greater myelin pathology in iNOS-deficient mice than in wild-type mice. Figure 2 describes a statistically significant increase in demyelination at 3 and 3.5 weeks; the difference disappeared by 4 weeks, so the finding concerns early demyelination. (LLM, conf=0.92)

  cites Arnett et al., 2002 source

In the paper

“indicating the complexity of growth factor fine tuning and interplay.”

What the sources say

• Supported

  The Discussion describes regulating exogenous and endogenous signalling as a major challenge in sequential growth-factor delivery. It also reports that BMP4–Noggin and BMP4–IGF-1 affected oligodendrocytes, astrocytes and remyelination differently, supporting the citing sentence’s interpretation that their effects require fine tuning and involve interplay. (LLM, conf=0.90)

  cites Sabo et al., 2013 source

In the paper

“Conversely, infusion of Noggin, an antagonist of the BMP4-pathway, promoted maturation of oligodendrocytes and potentiated remyelination in the CC after cuprizone withdrawal (Sabo et al., 2011).”

What the sources say

• Supported

  The Discussion identifies Noggin as a BMP4 antagonist and reports more mature oligodendrocytes and enhanced remyelination following recovery. The results sections report increased mature oligodendrocytes and myelinated axons in the corpus callosum after cuprizone challenge. Noggin was infused during the challenge; the reported effects were measured after withdrawal. (LLM, conf=0.94)

  cites Sabo et al., 2011 source

In the paper

“The results of the study by Sabo et al. indicated an important role for bone morphogenic protein (BMP) in modulating oligodendrogliogenesis and remyelination (Sabo et al., 2011).”

What the sources say

• Supported

  The Discussion explicitly concludes that BMP signaling has an important role in modulating oligodendrogliogenesis and remyelination. It reports that inhibiting endogenous BMP signaling during demyelination promoted mature oligodendrocyte regeneration and myelin repair. (LLM, conf=0.95)

  cites Sabo et al., 2011 source

In the paper

“The BMP-pathway was also activated in astrocytes and Olig2-positive cells during cuprizone-induced demyelination (Sabo et al., 2011).”

What the sources say

• Supported

  The section “Demyelination within the corpus callosum influences BMP signaling” reports increased BMP signaling after cuprizone challenge, with pSMAD1/5/8 labeling in Olig2-positive cells and a subset of GFAP-positive astrocytes. The Discussion likewise states that BMP signaling is active in OPCs and astrocytes in the demyelinated corpus callosum. (LLM, conf=0.94)

  cites Sabo et al., 2011 source

In the paper

“However, the sequential delivery of BMP4 between weeks 4 and 5 followed by Noggin infusion for the following week did not improve remyelination (Sabo et al., 2013)”

What the sources say

• Supported

  The Experimental Procedures (Figure 1; page unavailable) specify BMP4 infusion for seven days after week 4 of cuprizone challenge, followed by seven days of Noggin infusion. The Results (Figure 5; page unavailable) report that this sequential delivery did not enhance remyelination following recovery. (LLM, conf=0.94)

  cites Sabo et al., 2013 source

In the paper

“An intraventricular delivery of BMP4 for 7–14 days (4–5 or 4–6 week of cuprizone diet) transiently increased the proliferation predominantly of OPC and to a lower degree of astrocytes and microglia.”

What the sources say

• Partly supported

  The short-term infusion Results report increased proliferation of OPCs, microglia and astrocytes after 5 days of BMP4 infusion; the modulation Results also report increased proliferating oligodendroglial cells after 14 days. The Discussion describes OPC proliferation as predominant and notes that oligodendroglial numbers fell after a week of recovery. The stated 7-day delivery period is not supported: the shorter infusion lasted 5 days. Page numbers were not provided in our copy. (LLM, conf=0.87)

  cites Sabo et al., 2011 sourceExperimental — accuracy not yet measured

In the paper

“In our own study we were able to show that LIF mRNA expression was up-regulated very early mainly during the first 3 weeks of cuprizone administration in both CC and cortex thereafter decreasing to normal levels in the recovery phase after toxin withdrawal (Gudi et al., 2011).”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Gudi et al., 2011 sourceExperimental — accuracy not yet measured

In the paper

“suggesting a TNF-α-mediated mechanism of remyelination via astrocytic CXCL12 (Patel et al., 2012).”

What the sources say

• Supported

  The Discussion’s Fig. 7 describes a TNF-α-mediated remyelination mechanism in which astrocyte TNFR2 activation induces CXCL12, promoting oligodendrocyte progenitor proliferation and differentiation. The claim appropriately presents this as a suggested mechanism. Page numbers were not supplied. (LLM, conf=0.94)

  cites Patel et al., 2012 source

In the paper

“The lentiviral-gene delivery of CXCL12 into TNFR2 −/− mice could rescue this effect”

What the sources say

• Supported

  The Results section, “Delivery of CXCL12-encoding lentivirus rescues remyelination,” reports that CXCL12 lentivirus increased OPC proliferation and MBP expression in TNFR2-deficient mice compared with empty-vector lentivirus. The authors conclude that CXCL12 reinstatement improved remyelination in mice with CPZ-induced demyelination. (LLM, conf=0.94)

  cites Patel et al., 2012 source

In the paper

“Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia.”

In the paper

“Recently we have shown that especially differentiated oligodendrocytes but not OPC are affected by cuprizone in vitro (Benardais et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Benardais et al., 2013 source

In the paper

“Our studies suggested that this process may be regulated by the chemokine CXCL10 since CXCL10 mRNA expression was reduced in the astrocyte-depleted mice”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“and the treatment of astrocyte cultures with LPS, IL-1β, or TNF-α led to an enhancement of CXCL10 production in vitro (Skripuletz et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“Interestingly, a partial ablation of astrocytes in mice challenged for 3 weeks with cuprizone did not reveal any difference in CCL2 and CCL3 expression”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“In line with other studies (McMahon et al., 2001; Buschmann et al., 2012) we could also detect an up-regulated expression of CCL2 and CCL3 upon cuprizone treatment (Skripuletz et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions.”

In the paper

“The dose of cuprizone is one of the most important factors to induce demyelination in the murine CNS.”

In the paper

“Remyelination rapidly progresses after termination of the cuprizone diet (acute demyelination, Figure 1).”

In the paper

“Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions.”

In the paper

“suggesting that the local cellular microenvironment can promote or prevent deleterious effects of cuprizone and demyelination and remyelination.”

In the paper

“In the light of all these evidences it is obvious that cuprizone directly or indirectly impairs a variety of essential cell functions.”

In the paper

“Although EAE is probably the most commonly used model that reflects the autoimmune origin of MS, toxic demyelination is more appropriate to study remyelination.”

In the paper

“Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination.”

In the paper

“Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells.”

In the paper

“Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions.”

In the paper

“Cuprizone [bis–cyclohexanone-oxaldihydrazone] is a copper chelating reagent, which supplemented to normal rodent chow, directly or indirectly causes oligodendroglial cell death with subsequent demyelination.”

In the paper

“Thus, the cuprizone model is a suitable tool to study basic glial reactions and interactions during de- and re-myelination in absence of primarily immune-mediated mechanisms.”

In the paper

“When cuprizone is fed continuously remyelination is abortive and demyelination persists till the end of the diet (chronic demyelination).”

In the paper

“However, copper administration (100 ppm) synchronously to cuprizone administration (0.5%) did not reduce the toxic effects (Carlton, 1967).”

What the sources say

• ?Not checked — no full text of the sourcecites Carlton, 1967 source

In the paper

“Axonal damage and glial response accompanying demyelination were more severe and prolonged in aged (6–7 months) as compared to young (8–10 weeks) mice (Irvine and Blakemore, 2006).”

What the sources say

• ?Not checked — no full text of the sourcecites Irvine and Blakemore, 2006 source

In the paper

“Thus, 0.2% (w/w) cuprizone was established to induce highly reproducible and extensive demyelination without detrimental systemic effects in 8–10 weeks old mice.”

What the sources say

• ?Not checked — no full text of the sourcecites Hiremath et al., 1998 source

In the paper

“Since p75NTR −/− mice did not show any alteration regarding the course of de- and remyelination or glial reactions it is obvious that p75NTR does not play a major role in the induction of apoptosis in the cuprizone model.”

What the sources say

• ?Not checked — no full text of the sourcecites Copray et al., 2005 source

In the paper

“However, mitochondrial disturbances seem to be the key factor of oligodendroglial apoptosis, since enlarged “giant” mitochondria were detected in the liver and brain of cuprizone-treated mice (Suzuki, 1969; Hemm et al., 1971; Komoly et al., 1987).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Suzuki, 1969
• ?Not checked — no full text of the sourcecites Hemm et al., 1971 source
• ?Not checked — no full text of the sourcecites Komoly et al., 1987 source

In the paper

“However, it always has to be kept in mind, that cuprizone-induced oligodendroglial cell death followed by myelin clearance is an artificial event directly or indirectly caused by this toxin.”

In the paper

“Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions.”

In the paper

“Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells.”

In the paper

“Furthermore, demyelination may also be detected in other brain regions such as hippocampus, basal ganglia, and cerebellum (Koutsoudaki et al., 2009; Pott et al., 2009; Skripuletz et al., 2010a).”

What the sources say

• ?Not checked — no full text of the sourcecites Koutsoudaki et al., 2009 source
• ?Not checked — no full text of the sourcecites Pott et al., 2009 source
• ?Not checked — no full text of the sourcecites Skripuletz et al., 2010a source

In the paper

“Once demyelination is complete new oligodendrocytes, generated from the pool of oligodendrocyte progenitors (OPC), begin to form new myelin sheaths.”

In the paper

“Kotter and colleagues, who demonstrated a delayed OPC recruitment after the depletion of macrophages via exposure of mice to clodronate-liposomes prior/after lysolecithin-induced demyelination.”

What the sources say

• ?Not checked — no full text of the sourcecites Kotter et al., 2001 source
• ?Not checked — no full text of the sourcecites Kotter et al., 2005 source

In the paper

“In the acute cuprizone model activated microglia appear already at the first 2 weeks even before demyelination can be detected by histology and immunohistochemistry (Hiremath et al., 1998) (Figure 2).”

What the sources say

• ?Not checked — no full text of the sourcecites Hiremath et al., 1998 source

In the paper

“It seems that in the case of continued cuprizone feeding until week 6 newly generated oligodendrocytes are damaged again.”

In the paper

“The most representative type of microglia during demyelination expressed CD11b+/CD45low (CD, cluster of differentiation) and displayed a high ex vivo phagocytic activity accompanied by up-regulation of several phagocytic receptors such as Trem2b, FcγR II/III, CD36, and Tim-3 (Voss et al., 2012)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Voss et al., 2012

In the paper

“The authors linked this phenomenon to an altered growth factor expression in macrophage-depleted animals (Kotter et al., 2001, 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Kotter et al., 2001 source
• ?Not checked — no full text of the sourcecites Kotter et al., 2005 source

In the paper

“suggesting that phagocytosis is one of the most prominent features of microglia in the cuprizone model”

In the paper

“The expression of MHC class II was significantly increased at the maximum of demyelination (week 5) in both the CC and the cortex (Voss et al., 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Voss et al., 2012

In the paper

“After 3 weeks activated microglia are numerously present in the CC, cortex, and hippocampus.”

In the paper

“and remyelination was accelerated in ST8 alpha-N-Acetyl-Neuraminide alpha-2,8-Sialyltransferase 4 (St8siaIV, the polysialyltransferase responsible for PSA synthesis) knockout mice (Koutsoudaki et al., 2010), suggesting that these molecular mechanisms are indeed involved in remyelination.”

What the sources say

• ?Not checked — no full text of the sourcecites Koutsoudaki et al., 2010 source

In the paper

“TNF-α production was strongly increased during primary demyelination in both white and gray matter microglia.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Voss et al., 2012

In the paper

“The extent of microglial accumulation during cuprizone-induced demyelination is not uniform as well.”

In the paper

“These repair mechanisms start very early even before demyelination can be detected immunohistochemically.”

In the paper

“However, the remyelination capacity was clearly reduced after the withdrawal of cuprizone (Ludwin, 1980; Lindner et al., 2009).”

What the sources say

• ?Not checked — no full text of the sourcecites Ludwin, 1980
• ?Not checked — no full text of the sourcecites Lindner et al., 2009 source

In the paper

“Cerebellar gray and white matter shows severe demyelination after 12 weeks of cuprizone feeding (Skripuletz et al., 2010a).”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2010a source

In the paper

“suggesting that these molecular mechanisms are indeed involved in remyelination.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Mi et al., 2009
• ?Not checked — no full text of the sourcecites Koutsoudaki et al., 2010 source

In the paper

“Conspicuously, following cuprizone-induced demyelination the peak of microglial activation tightly correlates with a massive accumulation of OPC.”

In the paper

“It is important to mention that degradation/re-expression of different myelin proteins (at least in the CC and as depicted by immunohistochemistry) follows individual temporal pattern (Gudi et al., 2009).”

What the sources say

• ?Not checked — no full text of the sourcecites Gudi et al., 2009 source

In the paper

“In the next 2–3 weeks highly activated and proliferating microglia clear myelin debris.”

In the paper

“In contrast, TGF-β, IFN-γ, IL-12, and IL-10 were not regulated (Voss et al., 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Voss et al., 2012

In the paper

“Already in the 1960s Carlton reported that cuprizone ingestion in mice led to enlargement and hyperplasia of astroglia in brain regions that showed signs of cuprizone-induced demyelination”

What the sources say

• ?Not checked — no full text of the sourcecites Carlton, 1967 source

In the paper

“Since astrocytes show significantly lower gene and protein expression of GFAP after chronic demyelination compared to acute demyelination”

What the sources say

• ?Not checked — no full text of the sourcecites Ludwin, 1980
• ?Not checked — no full text of the sourcecites Kipp et al., 2011b source

In the paper

“but resulted in a diminished activation and invasion of microglia into the demyelinated lesion.”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“Concomitantly, astrocytes display signs of proliferation during the course of acute demyelination (Hiremath et al., 1998; Gudi et al., 2009).”

What the sources say

• ?Not checked — no full text of the sourcecites Hiremath et al., 1998 source
• ?Not checked — no full text of the sourcecites Gudi et al., 2009 source

In the paper

“The number of astrocytes is not significantly increased until 3 weeks of cuprizone treatment, simultaneously with first signs of apparent demyelination.”

In the paper

“and that astrocytosis preceded loss of myelin (Carlton, 1967)”

What the sources say

• ?Not checked — no full text of the sourcecites Carlton, 1967 source

In the paper

“indicating a potential beneficial role of FABP7 expression in activated astrocytes for remyelination.”

In the paper

“suggesting that the co-stimulatory capacity of microglia in the cuprizone model was not sufficient to activate T cells”

In the paper

“Interestingly, the expression of FABP7 in astrocytes also correlated with remyelination of lesions in EAE and MS”

In the paper

“It was concluded, that astrocytes are responsible for the recruitment of microglia.”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“Our own study revealed that 5–7% of CD11b+/CD45high cells were present in the CC at week 5 and 6, even 1 week after cuprizone diet cessation (Voss et al., 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Voss et al., 2012

In the paper

“and induced the expression of various growth factors in vitro [FGF2, PDGFα, and osteopontin (OPN)]”

In the paper

“the activation status of astrocytes appears to be higher after acute demyelination (Ludwin, 1980; Kipp et al., 2011b)”

What the sources say

• ?Not checked — no full text of the sourcecites Ludwin, 1980
• ?Not checked — no full text of the sourcecites Kipp et al., 2011b source

In the paper

“macrophages constituted 1–4% of the RCA-1+ population at week 5–6 of cuprizone exposure (McMahon et al., 2002)”

What the sources say

• ?Not checked — no full text of the sourcecites McMahon et al., 2002 source

In the paper

“CD200R was rather up-regulated during early demyelination (Voss et al., 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Voss et al., 2012

In the paper

“In contrast, the expression of endogenous antagonists of metalloproteinases (TIMP) was increased during the demyelination peak between weeks 4.5 and 5.”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“suggesting that beneficial effects of TNF-α on proliferation of OPC and subsequent remyelination are promoted through the TNFR2 pathway (Arnett et al., 2001).”

What the sources say

• ?Not checked — no full text of the sourcecites Arnett et al., 2001 source

In the paper

“MMP12 was additionally up-regulated during the demyelination phase”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“In the cuprizone model, Lt-α is expressed primarily by astroglia (Plant et al., 2005)”

What the sources say

• ?Not checked — no full text of the sourcecites Plant et al., 2005 source

In the paper

“MMP3 was localized exclusively in activated astrocytes”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“In this study TNFR2 but not TNFR1 has been shown to be gradually up-regulated during de- and remyelination (Arnett et al., 2001).”

What the sources say

• ?Not checked — no full text of the sourcecites Arnett et al., 2001 source

In the paper

“There is increasing evidence that astrocytes are key players in complex interactions with OPC, mature oligodendrocytes, and microglia supporting remyelination at least in the cuprizone model.”

In the paper

“arguing for a regulatory role of MMP in tissue regeneration (Skuljec et al., 2011)”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“However, a growing body of evidence corroborates the assumption that an adequate and controlled inflammatory response is required for a successful myelin regeneration promoting the clearance of myelin debris and stimulating proliferation/regeneration of myelin-forming oligodendrocytes (Diemel et al., 1998; Robinson and Miller, 1999; Arnett et al., 2001; Kotter et al., 2001, 2005, 2006; Setzu et al”

What the sources say

• ?Not checked — no full text of the sourcecites Diemel et al., 1998 source
• ?Not checked — no full text of the sourcecites Arnett et al., 2001 source
• ?Not checked — no full text of the sourcecites Kotter et al., 2001 source

In the paper

“Previously, our group could show significant changes in the expression of several MMP, especially during the remyelination phase, arguing for a regulatory role of MMP in tissue regeneration (Skuljec et al., 2011).”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“The course of remyelination was not influenced by this mutation.”

What the sources say

• ?Not checked — no full text of the sourcecites Plant et al., 2005 source

In the paper

“whereas the source of TIMP1 in the CNS is linked to astrocytes (Gardner and Ghorpade, 2003).”

What the sources say

• ?Not checked — no full text of the sourcecites Gardner and Ghorpade, 2003 source

In the paper

“Previously, OPN was shown to be up-regulated in MS lesions and in several experimental animal models for demyelination including the cuprizone model (Chabas et al., 2001; Selvaraju et al., 2004; Zhao et al., 2008).”

What the sources say

• ?Not checked — no full text of the sourcecites Chabas et al., 2001 source
• ?Not checked — no full text of the sourcecites Selvaraju et al., 2004 source
• ?Not checked — no full text of the sourcecites Zhao et al., 2008 source

In the paper

“however, MMP7, -9, -11, -13, -15 were either not regulated or even down-regulated during myelin clearance in the CC.”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“In addition, the depletion of astrocytes resulted in diminished numbers of mature oligodendrocytes during remyelination (Skripuletz et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“Furthermore, similar to TNF-α-deficient mice TNFR2 −/− mice displayed diminished/delayed regeneration of myelin”

What the sources say

• ?Not checked — no full text of the sourcecites Arnett et al., 2001 source

In the paper

“TIMP2 was found to be expressed by microglia (Skuljec et al., 2011)”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“In particular, the expression of MMP11, MMP12, and MMP3 was clearly increased during remyelination.”

What the sources say

• ?Not checked — no full text of the sourcecites Skuljec et al., 2011 source

In the paper

“It seems, however, that in the cuprizone model deleterious effects of MMP and inflammatory processes themselves are tightly controlled by TIMP.”

In the paper

“In conclusion, these conflicting results may allow the assumption that the effects of IFN-γ and other pro-inflammatory molecules, whether harmful or helpful, are dependent on their quantitative and temporal expression pattern.”

In the paper

“Being a potent mitogen for OPC PDGFα is one of the prominent compounds of the culture medium of primary cortical OPC derived from new-borns or embryos as well as immortalized OPC in vitro (Noble et al., 1988; Bansal et al., 1996).”

What the sources say

• ?Not checked — no full text of the sourcecites Noble et al., 1988 source
• ?Not checked — no full text of the sourcecites Bansal et al., 1996 source

In the paper

“Differentiation of OPC was, however, not altered in PDGFαR +/− mice (Murtie et al., 2005b).”

What the sources say

• ?Not checked — no full text of the sourcecites Murtie et al., 2005b source

In the paper

“Upon cuprizone treatment the expression of OPN was increased on the peak of demyelination and during early remyelination in activated astrocytes and microglia.”

In the paper

“arguing for an important role of PDGFαR-signaling on OPC proliferation.”

What the sources say

• ?Not checked — no full text of the sourcecites Murtie et al., 2005b source

In the paper

“The positive effect of IGF-1 on mature oligodendrocyte survival was also observed in vitro (Barres et al., 1992, 1993; Ye and D'Ercole, 1999).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Barres et al., 1992, 1993; Ye and D'Ercole, 1999

In the paper

“In our own studies we could confirm this finding; however, additionally we observed IGF-1 mRNA expression in activated microglia (Voss et al., 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Voss et al., 2012

In the paper

“Since there was no significant enhancement of remyelination in the lysolecithin model the authors concluded, that the OPC density seems not to be a rate-limiting factor for a successful remyelination (Woodruff et al., 2004).”

What the sources say

• ?Not checked — no full text of the sourcecites Woodruff et al., 2004 source

In the paper

“Another study showed an impaired oligodendrocyte repopulation in PDGFαR heterozygous knockout mice, caused by a reduced proliferation capacity and overall density of OPC arguing for an important role of PDGFαR-signaling on OPC proliferation.”

What the sources say

• ?Not checked — no full text of the sourcecites Murtie et al., 2005b source

In the paper

“Interestingly, microgliosis was more pronounced in mice that constantly over-expressed IGF-1 within the brain after 3 weeks of cuprizone diet (Mason et al.,”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Mason et al.

In the paper

“LPS, IL-1β, and TNF-α-induced CCL2 secretion by astrocytes, but not microglia in vitro (Hayashi et al., 1995).”

What the sources say

• ?Not checked — no full text of the sourcecites Hayashi et al., 1995 source

In the paper

“suggesting an important role for BMP-signaling in demyelinating events.”

What the sources say

• ?Not checked — no full text of the sourcecites Ara et al., 2008 source

In the paper

“arguing for astrocyte-derived factors that mediate attraction of microglia.”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“In vivo, the expression of BMP4 was elevated in OPC within demyelinated lesions induced by ethidium bromide (Zhao et al., 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Zhao et al., 2005 source

In the paper

“In cuprizone-induced demyelination CCL2 expression was a transient phenomenon (McMahon et al., 2001; Buschmann et al., 2012) being significantly up-regulated particularly during the first week of cuprizone exposure.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites McMahon et al., 2001; Buschmann et al., 2012

In the paper

“Our studies suggested that this process may be regulated by the chemokine CXCL10”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“suggesting that these cytokines are not astrocyte-derived at least at this time point (Skripuletz et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Skripuletz et al., 2013 source

In the paper

“Upon cuprizone-induced demyelination mRNA expression of chemokine CCL3 was initiated already after 2 days and then gradually increased until week 4 (McMahon et al., 2001; Buschmann et al., 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites McMahon et al., 2001; Buschmann et al., 2012

In the paper

“However, remyelination was not further enhanced if wt mice were complemented with LIF during the recovery phase (Marriott et al., 2008).”

What the sources say

• ?Not checked — no full text of the sourcecites Marriott et al., 2008 source

In the paper

“and can prevent oligodendrocyte death under pro-inflammatory conditions in vitro (Louis et al., 1993; Vartanian et al., 1995).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Louis et al., 1993; Vartanian et al., 1995

In the paper

“Remarkably, the oligodendrocyte replenishment, which includes both OPC proliferation and differentiation, seemed not to be significantly compromised in these transgenic mice”

What the sources say

• ?Not checked — no full text of the sourcecites Marriott et al., 2008 source

In the paper

“Additionally, this study showed that CCL2 induces chemotaxis of microglia.”

What the sources say

• ?Not checked — no full text of the sourcecites Hayashi et al., 1995 source

In the paper

“Similarly, in EAE BMP4 was up-regulated upon demyelination (Ara et al., 2008)”

What the sources say

• ?Not checked — no full text of the sourcecites Ara et al., 2008 source

In the paper

“The assessment of remyelination is complicated in EAE and in virus mediated models due to concurrently occurring de- and remyelination.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Table 1

In the paper

“Another drawback of autoimmune-induced demyelination is the unpredictable localization of lesions that classically occur in the spinal cord.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Table 1

In the paper

“Thus, similar to other toxin-induced demyelination models, lesion induction is probably not relevant to MS”

In the paper

“Activation of the CXCR4 cascade in OPC leads to migration, proliferation, and differentiation of these cells (Dziembowska et al., 2005; Kadi et al., 2006; Maysami et al., 2006).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Dziembowska et al., 2005; Kadi et al., 2006; Maysami et al., 2006

In the paper

“The cellular source of CXCL12 within the CC of cuprizone-treated mice includes both GFAP-positive astrocytes and CD11b-positive microglia.”

What the sources say

• ?Not checked — no full text of the sourcecites Patel et al., 2010 source

In the paper

“In the adult CNS, CXCL12 orchestrates neurotransmission, neurotoxicity and neuroglial interactions (Lazarini et al., 2003).”

What the sources say

• ?Not checked — no full text of the sourcecites Lazarini et al., 2003 source

In the paper

“Toxic models are commonly used to study remyelination since their kinetics are well predictable and the lesion site is known.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Table 1

In the paper

“the cuprizone model becomes increasingly attractive to study the underlying pathophysiological mechanisms of de- and remyelination to uncover regional differences (Gudi et al., 2009; Pott et al., 2009; Schmidt et al., 2013).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Gudi et al., 2009; Pott et al., 2009; Schmidt et al., 2013

In the paper

“However, it was already described in the early work by the group of Matsushima and confirmed by others that complete demyelination of the CC occurs at week 5 of cuprizone feeding.”

In the paper

“Remyelination is fast and robust after acute demyelination (cuprizone feeding for 5 weeks).”

In the paper

“Moreover, known immunosuppressive therapeutics that are quite effective in relapsing-remitting MS (RRMS) extend limited beneficial effects during late stages of secondary-progressive (SPMS) and primary-progressive (PPMS) MS subtypes (Bradl and Lassmann, 2009).”

What the sources say

• ?Not checked — no full text of the sourcecites Bradl and Lassmann, 2009 source

In the paper

“Another plus of these models is a clear read-out of remyelination since significant improvements of remyelination can be gradually reflected by functional recovery of the animals.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Table 1

In the paper

“since recent studies have shown that the de- and remyelination extend as well the cellular composition seems to differ between white and gray matter MS lesions (Bo et al., 2003; Albert et al., 2007; Van Horssen et al., 2007)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bo et al., 2003; Albert et al., 2007; Van Horssen et al., 2007

In the paper

“A recent study provided insights that even 2–3 weeks of cuprizone ingestion is sufficient to induce glial responses and de- and remyelination pattern similar to that described for 5–6 week treatment (Doan et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Doan et al., 2013 source