Live imaging of remyelination after antibody-mediated demyelination in an ex-vivo model for immune mediated CNS damage

Harrer, Melanie D.; Büdingen, Hans‐Christian von; Stoppini, Luc; Alliod, Chantal; Pouly, Sandrine; Fischer, Katja; Goebels, Norbert

doi:10.1016/j.expneurol.2008.12.027

Cited by 27 publications

(31 citation statements)

References 45 publications

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“…Addition of anti-white matter serum with complement also demyelinated spinal cord slices, and IGF-1 both inhibited this and accelerated remyelination as defined by a return of CNPase activity (Roth et al, 1995). Anti-MOG antibody in combination with complement demyelinates mouse cerebellar slices as shown by loss of MBP-positive immunofluorescence and ELISA specific for MBP (Harrer et al, 2009). Theiler virus added to myelinated mouse spinal cord cultures caused marked demyelination (Shahar et al, 1986).…”

Section: Demyelinationmentioning

confidence: 98%

“…Direct visualization of myelinating cells in slice cultures can be achieved using transgenic mice expressing a fluorescent protein under an oligodendrocyte promoter (e.g. PLP-GFP) (Harrer et al, 2009). Delivery of genes, e.g.…”

Section: Mutant/transgenic Micementioning

confidence: 99%

“…Similarly, an approach using a b-galactosidase luminometric assay in a transgenic mouse expressing LacZ under the MBP promoter only measures MBP expression rather than the formation of myelin sheaths . Competitive inhibition ELISA was developed to measure the amount of MBP, found in both mature oligodendrocytes and the myelin sheath, in cerebellar explant cultures and found a 90% decrease in MBP on demyelination (Harrer et al, 2009;Nishimura et al, 1986). Myelin proteins, such as MBP, PLP/DM20, MAG, MOG, and CNPase, can also be measured by western blot from cultures (Brinkmann et al, 2008;Mi et al, 2009) as a surrogate marker of myelination.…”

Section: Quantificationmentioning

confidence: 99%

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In vitro modeling of central nervous system myelination and remyelination

Jarjour¹,

Zhang²,

Bauer³

et al. 2011

Glia

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This review aims to summarize the current techniques to study myelination and remyelination in culture systems. We attempt to put these into historical context, and to identify the strengths and weaknesses of each approach, which vary depending on the experimental question to be tested. We discuss the difficulty and importance of quantification of myelination and in particular remyelination. Finally, we provide our predictions of how these techniques will and should develop in the future.

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Section: Demyelinationmentioning

confidence: 98%

Section: Mutant/transgenic Micementioning

confidence: 99%

Section: Quantificationmentioning

confidence: 99%

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In vitro modeling of central nervous system myelination and remyelination

Jarjour¹,

Zhang²,

Bauer³

et al. 2011

Glia

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“…19 For primary antibodies monoclonal mouse anti-murine neurofilament 200 antibody (clone N52; Sigma-Aldrich, Buchs, Switzerland), monoclonal rat anti-murine MHC class I (clone ER-HR52; BMA Biomedicals, August, Switzerland), monoclonal rat anti-murine MHC class II (clone M5/114.15.2, BD Biosciences, Oxford, UK), and monoclonal rat antimurine myelin basic protein (Serotec, Düsseldorf, Germany) were used as indicated and were detected with secondary goat anti-mouse Alexa Fluor 405-conjugated antibody or goat anti-rat Alexa Fluor 594-conjugated antibody (both by Invitrogen). …”

Section: Immunostainingmentioning

confidence: 99%

Collateral Bystander Damage by Myelin-Directed CD8+ T Cells Causes Axonal Loss

Sobottka

Harrer

Ziegler

et al. 2009

The American Journal of Pathology

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Permanent disability of patients suffering from central nervous system (CNS) inflammation such as multiple sclerosis, the most common chronic inflammatory disorder of the CNS, originates mainly from demyelination and axonal damage. Although many studies in the past focused on the role of CD4 ؉ T cells, several recent findings postulate the relevance of autoaggressive, cytotoxic CD8 ؉ T cells in the effector phase of multiple sclerosis. Yet, it remains unresolved whether axonal injury is the result of a CD8 ؉ T cell-targeted hit against the axon itself or the consequence of an attack against the myelin structure. To address this issue of CD8-mediated tissue damage in CNS inflammation , we performed continuous confocal imaging of autoaggressive , cytotoxic CD8 ؉ T cells in living organotypic cerebellar brain slices. We observed that loading brain slices with the cognate peptide antigen caused CD8-mediated damage of myelinated axons. To exclude the possibility that the cognate peptide loaded onto the brain slices was presented by axons directly , we restricted the cognate antigen expression exclusively to the cytosol of oligodendrocytes. Aside from vast myelin damage , extensive axonal bystander injury occurred. Using this model system of inflammatory CNS injury , we visualize that axonal loss can be the consequence from "collateral bystander damage" by autoaggressive , cytotoxic CD8 ؉ T cells , targeting their cognate antigen processed and presented by oligodendrocytes.

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“…Ex vivo preparations used to image OL process dynamics, axon interactions and myelination comprise acute (Haberlandt et al, 2011) and cultured brain slices (Haber et al, 2009;Harrer et al, 2009), and spinal cord explants (Ioannidou et al, 2012). Viable slice cultures of CNS tissue can be maintained in culture for a number of weeks (Haber et al, 2009;De Simoni and Yu, 2006), and so provide ample opportunities to observe OL and axon dynamics at time-points remote enough from slice preparation to avoid the influence of slice-associated injuries.…”

Section: Ex Vivo Cns Tissue Systemsmentioning

confidence: 99%

Live-imaging in the CNS: New insights on oligodendrocytes, myelination, and their responses to inflammation

2016

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The formation and repair of myelin involves alterations in the molecular and physical properties of oligodendrocytes, and highly coordinated interactions with their target axons. Characterising the nature and timing of these events at the molecular and cellular levels illuminates the fundamental events underlying myelin formation, and provides opportunities for the development of therapies to replace myelin lost through traumatic injury and inflammation. The dynamic nature of these events requires that live-imaging methods be used to capture this information accurately and completely. Developments in imaging technologies, and model systems suitable for their application to myelination, have advanced the study of myelin formation, injury and repair. Similarly, new techniques for single molecule imaging, and novel imaging probes, are providing opportunities to resolve the dynamics of myelin proteins during myelination. Here, we explore these developments in the context of myelin formation and injury, identify unmet needs within the field where progress can be advanced through live-imaging approaches, identify technical challenges that are limiting this progress, and highlight practical applications for these approaches that could lead to therapies for the protection of oligodendrocytes and myelin from injury, and restore myelin lost through injury and disease. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.

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Live imaging of remyelination after antibody-mediated demyelination in an ex-vivo model for immune mediated CNS damage

Cited by 27 publications

References 45 publications

In vitro modeling of central nervous system myelination and remyelination

In vitro modeling of central nervous system myelination and remyelination

Collateral Bystander Damage by Myelin-Directed CD8+ T Cells Causes Axonal Loss

Live-imaging in the CNS: New insights on oligodendrocytes, myelination, and their responses to inflammation

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