Moving beyond the glial scar for spinal cord repair

Bradbury, Elizabeth J.; Burnside, Emily R.

doi:10.1038/s41467-019-11707-7

Cited by 469 publications

(434 citation statements)

References 180 publications

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“…Accumulating findings have suggested the critical role of the ECM in SCI (Klapka and Müller, 2006;Schwab and Strittmatter, 2014;Yokota et al, 2017). ECM molecules not only directly participate in neuronal loss, inflammatory infiltration and axonal dieback/regrowth but also determine the outcomes of SCI by modulating scar-forming astrocytes and other cell types (Gaudet and Popovich, 2014;Didangelos et al, 2016;Bradbury and Burnside, 2019). As mentioned before, astrocytes exhibit high environment-dependent plasticity and are highly influenced by ECM molecules.…”

Section: Environmental Regulation Of Astrocytic Fatementioning

confidence: 92%

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Yang

Dai

Chen

et al. 2020

Front. Cell. Neurosci.

146

161

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Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of the SCI lesion, the glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. In recent years, it has become increasingly accepted that the glial scar plays a dual role in SCI recovery. However, the underlying mechanisms of this dual role are complex and need further clarification. This dual role also makes it difficult to manipulate the glial scar for therapeutic purposes. Here, we briefly discuss glial scar formation and some representative components associated with scar-forming astrocytes. Then, we analyze the dual role of the glial scar in a dynamic perspective with special attention to scar-forming astrocytes to explore the underlying mechanisms of this dual role. Finally, taking the dual role of the glial scar into account, we provide several pieces of advice on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.

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Section: Environmental Regulation Of Astrocytic Fatementioning

confidence: 92%

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Yang

Dai

Chen

et al. 2020

Front. Cell. Neurosci.

146

161

View full text Add to dashboard Cite

show abstract

“…Efforts to prevent or dissociate the glial scar have been shown to improve axon regeneration (for example, see Rosenzweig et al, 2019). However, the biology of the glial scar is much more nuanced, and oversimplification of this complex healing and regeneration process can hinder advances in the field (Bradbury and Burnside, 2019). Therefore, a detailed understanding of the players involved, including the glial subtypes, can provide additional clues for intervention.…”

Section: Modulating Glial Cell-axonal Growth Cone Interactions To Aidmentioning

confidence: 99%

Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration

2020

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The developing nervous system is a complex yet organized system of neurons, glial support cells, and extracellular matrix that arranges into an elegant, highly structured network. The extracellular and intracellular events that guide axons to their target locations have been well characterized in many regions of the developing nervous system. However, despite extensive work, we have a poor understanding of how axonal growth cones interact with surrounding glial cells to regulate network assembly. Gliato-growth cone communication is either direct through cellular contacts or indirect through modulation of the local microenvironment via the secretion of factors or signaling molecules. Microglia, oligodendrocytes, astrocytes, Schwann cells, neural progenitor cells, and olfactory ensheathing cells have all been demonstrated to directly impact axon growth and guidance. Expanding our understanding of how different glial cell types directly interact with growing axons throughout neurodevelopment will inform basic and clinical neuroscientists. For example, identifying the key cellular players beyond the axonal growth cone itself may provide translational clues to develop therapeutic interventions to modulate neuron growth during development or regeneration following injury. This review will provide an overview of the current knowledge about glial involvement in development of the nervous system, specifically focusing on how glia directly interact with growing and maturing axons to influence neuronal connectivity. This focus will be applied to the clinically-relevant field of regeneration following spinal cord injury, highlighting how a better understanding of the roles of glia in neurodevelopment can inform strategies to improve axon regeneration after injury.

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“…These data may well reflect, the differences in ECM composition in different regions and injury conditions. Extracellular matrix changes have mostly been examined after spinal cord injury aiming to understand how they affect the restoration of ascending and descending axonal connections (Didangelos et al, 2016;Bradbury and Burnside, 2019). Several ECM components have been found to be inhibitory for repair, especially chondroitin sulfate glycosaminoglycan-chains (GAGchains) on proteoglycans at the injury site.…”

mentioning

confidence: 99%

Filling the Gaps – A Call for Comprehensive Analysis of Extracellular Matrix of the Glial Scar in Region- and Injury-Specific Contexts

Kjell

Götz

2020

Front. Cell. Neurosci.

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Central nervous system (CNS) injury results in chronic scar formation that interferes with function and inhibits repair. Extracellular matrix (ECM) is prominent in the scar and potently regulates cell behavior. However, comprehensive information about the ECM proteome is largely lacking, and region-as well as injury-specific differences are often not taken into account. These aspects are the focus of our perspective on injury and scar formation. To highlight the importance of such comprehensive proteome analysis we include data obtained with novel analysis tools of the ECM composition in the scar and show the contribution of monocytes to the ECM composition after traumatic brain injury (TBI). Monocyte invasion was reduced using the CCR2-/-mouse line and stepwise de-cellularization and proteomics allowed determining monocyte-dependent ECM composition and architecture of the glial scar. We find significant reduction in the ECM proteins Tgm1, Itih (1,2, and 3), and Ftl in the absence of monocyte invasion. We also describe the scar ECM comprising zones with distinctive composition and show a subacute signature upon comparison to proteome obtained at earlier times after TBI. These results are discussed in light of injury-, region-and time-specific regulation of scar formation highlighting the urgent need to differentiate injury conditions and CNS-regions using comprehensive ECM analysis.

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Moving beyond the glial scar for spinal cord repair

Cited by 469 publications

References 180 publications

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration

Filling the Gaps – A Call for Comprehensive Analysis of Extracellular Matrix of the Glial Scar in Region- and Injury-Specific Contexts

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