Magnetic resonance imaging of experimental demyelinating lesions

Ford, Corey C.; Ceckler, Toni L.; Karp, Juliana; Herndon, Robert M.

doi:10.1002/mrm.1910140305

Cited by 21 publications

(9 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, a compensatory increase in aFn could explain the absence of a clear phenotype after pFn cKO , in agreement with studies of other tissues (Sakai et al, ). However, the observation that a + pFn cKO does not substantially amplify the reduction in OPC numbers during demyelination may support an alternative explanation, namely that excessive leakage of pFn to the demyelinated area does not occur on lysolecithin‐induced demyelination, despite breakdown of the blood‐brain barrier (Ford et al, ). Hence, in contrast to previous studies, in which pFn was considered a predominant source of the Fn matrix in tissue (Moretti et al, ), our findings indicate that aFn rather than pFn is the major component of the Fn matrix expressed after lysolecithin‐induced CNS demyelination.…”

Section: Discussionmentioning

confidence: 99%

The EIIIA domain from astrocyte‐derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination

Stoffels

Hoekstra

Franklin

et al. 2014

Glia

View full text Add to dashboard Cite

Central nervous system remyelination by oligodendrocyte progenitor cells (OPCs) ultimately fails in the majority of multiple sclerosis (MS) lesions. Remyelination benefits from transient expression of factors that promote migration and proliferation of OPCs, which may include fibronectin (Fn). Fn is present in demyelinated lesions in two major forms; plasma Fn (pFn), deposited following blood‐brain barrier disruption, and cellular Fn, synthesized by resident glial cells and containing alternatively spliced domains EIIIA and EIIIB. Here, we investigated the distinctive roles that astrocyte‐derived Fn (aFn) and pFn play in remyelination. We used an inducible Cre‐lox recombination strategy to selectively remove pFn, aFn or both from mice, and examined the impact on remyelination of toxin‐induced demyelinated lesions of spinal cord white matter. This approach revealed that astrocytes are a major source of Fn in demyelinated lesions. Furthermore, following aFn conditional knockout, the number of OPCs recruited to the demyelinated lesion decreased significantly, whereas OPC numbers were unaltered following pFn conditional knockout. However, remyelination completed normally following conditional knockout of aFn and pFn. Both the EIIIA and EIIIB domains of aFn were expressed following demyelination, and in vitro assays demonstrated that the EIIIA domain of aFn mediates proliferation of OPCs, but not migration. Therefore, although the EIIIA domain from aFn mediates OPC proliferation, aFn is not essential for successful remyelination. Since previous findings indicated that astrocyte‐derived Fn aggregates in chronic MS lesions inhibit remyelination, aFn removal may benefit therapeutic strategies to promote remyelination in MS. GLIA 2015;63:242–256

show abstract

Section: Discussionmentioning

confidence: 99%

The EIIIA domain from astrocyte‐derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination

Stoffels

Hoekstra

Franklin

et al. 2014

Glia

View full text Add to dashboard Cite

show abstract

“…22 The time span of the whole process depends on concentration of LPC and the injection procedure used. 8,23,24 LPC solution was infused into the ic area by stereotaxic microsurgery. Rats were anesthetized with intra-peritonial injection of sodium pentathal (40 mg/kg body weight) and fixed in the rat head-restraining stereotaxic surgical table.…”

Section: Lpc Injectionmentioning

confidence: 99%

Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)‐induced experimental demyelinating lesion model

et al. 2002

View full text Add to dashboard Cite

Metabolite changes in rat brain internal capsule (ic) area were monitored using volume localized in vivo proton MR spectroscopy (MRS) in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model of multiple sclerosis (MS), during the early phase (pre-acute) as well as during the complete pathological cycle of de- and re-myelination processes. The N-acetyl aspartate (NAA) peak showed reduction during the early phase of the lesion progression (demyelination) until day 10 and increased thereafter during remyelination. However, choline (Cho) and lipid resonances showed increased signal intensity during the early phase and decreased during remyelination. A progressive reduction of the NAA/Cr metabolite ratio in lesioned rats was observed during demyelination (up to day 10) compared with before lesion (control), and the value increased thereafter during remyelination (from day 15). During this period, however, the Cho/Cr ratio was a higher until day 10 and subsequently declined and was close to that calculated before lesion creation. The changes in NAA/Cr and Cho/Cr metabolite ratios correspond to changes in the individual metabolite peaks such as NAA and Cho. The increase in the intensity of the choline resonance during the early phase is indicative of the onset of an inflammatory demyelination process, and its rapid decrease thereafter is due to reduction in the inflammatory process associated with remyelination. Similarly, the increase in the intensity of lipids during the pre-acute stage of the lesion is attributed to active demyelination, which significantly decreased during remyelination. These MR results correlate well with the histology data obtained.

show abstract

“…Correlation of T2 relaxation with properties of the myelin sheath has been previously reported (Degaonkar et al, 2005; Ford et al, 1990; McArdle et al, 1987) but without assessment of WM morphology leaving unresolved the question of whether white matter T2 is mainly dependent on the cytoskeletal or myelination state. In the present study we have contrasted T2 relaxation times in two mouse models exhibiting selective myelin or axonal deficits, respectively.…”

Section: Introductionmentioning

confidence: 99%

The contributions of myelin and axonal caliber to transverse relaxation time in shiverer and neurofilament-deficient mouse models

Dyakin¹,

Chen²,

Branch³

et al. 2010

NeuroImage

View full text Add to dashboard Cite

White matter disorders can involve injury to myelin or axons but the respective contribution of each to clinical course is difficult to evaluate non-invasively. Here, to develop a paradigm for further investigations of axonal pathology by MRI, we compared two genetic mouse models exhibiting relatively selective axonal or myelin deficits using quantitative MRI relaxography of the transverse relaxation times (T2) in vivo and ultrastructural morphometry. In HM-DKO mice, which lack genes encoding the heavy (NF-H) and medium (NF-M) subunits of neurofilaments, neurofilament content of large myelinated axons of the central nervous system (CNS) is markedly reduced in the absence of changes in myelin thickness and volume. In shiverer mutant mice, which lack functional myelin basic protein, CNS myelin sheath formation is markedly reduced but neurofilament content is normal. We observed increases in T2 in nearly all white matter in Shiverer mice compared to their wild type, while more subtle increases in T2 were observed in HM-DKO in the corpus callosum. White matter T2 was generally greater in Shiverer mice than HM-DKO mice. Ultrastructural morphometry of the corpus callosum, which exhibited the greatest T2 differences, confirmed that total cross sectional area occupied by axons was similar in the two mouse models and that the major ultrastructural differences, determined by morphometry, were an absence of myelin and larger unmyelinated axons in shiverer mice and absence of neurofilaments in HM-DKO mice. Our findings indicate that T2 is strongly influenced by myelination state and axonal volume, while neurofilament structure within the intra-axonal compartment has a lesser effect upon single compartment T2 estimates.

show abstract

Magnetic resonance imaging of experimental demyelinating lesions

Cited by 21 publications

References 15 publications

The EIIIA domain from astrocyte‐derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination

The EIIIA domain from astrocyte‐derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination

Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)‐induced experimental demyelinating lesion model

The contributions of myelin and axonal caliber to transverse relaxation time in shiverer and neurofilament-deficient mouse models

Contact Info

Product

Resources

About