Modulation of both intrinsic and extrinsic factors additively promotes rewiring of corticospinal circuits after spinal cord injury

Spinal cord injury is a devastating disease which disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. Most injured neurons fail to regenerate in the central nervous system after injury. Multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration after injury. MicroRNAs can modulate multiple genes’ expression and are tightly controlled during nerve development or the injury process. Evidence has demonstrated that microRNAs and their signaling pathways play important roles in mediating axon regeneration and glial scar formation after spinal cord injury. This article reviews the role and mechanism of differentially expressed microRNAs in regulating axon regeneration and glial scar formation after spinal cord injury, as well as their therapeutic potential for promoting axonal regeneration and repair of the injured spinal cord.

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Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399409001288 ◽

2009 ◽

Vol 11 ◽

Cited By ~ 32

Author(s):

Fardad T. Afshari ◽

Sunil Kappagantula ◽

James W. Fawcett

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Spinal Cord Injury ◽

Nervous System ◽

Functional Recovery ◽

Extrinsic Factors ◽

Permanent Disability ◽

Intrinsic Factors ◽

Cord Injury ◽

The Central Nervous System

Spinal cord injury is one of the most devastating conditions that affects the central nervous system. It can lead to permanent disability and there are around two million people affected worldwide. After injury, accumulation of myelin debris and formation of an inhibitory glial scar at the site of injury leads to a physical and chemical barrier that blocks axonal growth and regeneration. The mammalian central nervous system thus has a limited intrinsic ability to repair itself after injury. To improve axonal outgrowth and promote functional recovery, it is essential to identify the various intrinsic and extrinsic factors controlling regeneration and navigation of axons within the inhibitory environment of the central nervous system. Recent advances in spinal cord research have opened new avenues for the exploration of potential targets for repairing the cord and improving functional recovery after trauma. Here, we discuss some of the important key molecules that could be harnessed for repairing spinal cord injury.

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Perceived influence of intrinsic/extrinsic factors on participation in life activities after spinal cord injury

Disability and Health Journal ◽

10.1016/j.dhjo.2018.03.004 ◽

2018 ◽

Vol 11 (4) ◽

pp. 583-590 ◽

Cited By ~ 4

Author(s):

John E. Cobb ◽

Jean Leblond ◽

Frédéric S. Dumont ◽

Luc Noreau

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Extrinsic Factors ◽

Cord Injury

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Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

10.1101/2021.12.20.473346 ◽

2021 ◽

Author(s):

Leilei Gong ◽

Yun Gu ◽

Xiaoxiao Han ◽

Chengcheng Luan ◽

Xinghui Wang ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Immune Cell ◽

Leading Edge ◽

Glial Scar ◽

Scar Formation ◽

Cns Injury ◽

Extrinsic Factors ◽

Cord Injury

Adult regeneration in spinal cord is poor in mammalian but remarkable in the neonatal mammals and some vertebrates, including fish and salamanders. Increasing evidences basis of this interspecies and ontogeny highlighted the pivotal roles of neuron extrinsic factors-the glial scar, which exert confusing inhibiting or promoting regeneration function, but the spatiotemporal ordering of cellular and molecular events that drive repair processes in scar formation remains poorly understood. Here, we firstly constructed tissue-wide gene expression measurements of mouse spinal cords over the course of scar formation using the spatial transcriptomics (ST) technology in Spinal cord injury (SCI) repair. We analyzed the transcriptomes of nearly 15449 spots from 32 samples and distinguished normal and damage response regions. Compared to histological changes, spatial mapping of differentiation transitions in spinal cord injury site delineated the possible trajectory between subpopulations of fibroblast, glia and immune cell more comprehensively and defined the extent of scar boundary and core more accurately. Locally, we identified gene expression gradients from leading edge to the core of scar areas that allow for re-understanding of the scar microenvironment and found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophage, CD36 and Postn in fibroblast, Plxnb2 and Nxpe3 in microglia, Clu in astrocyte and CD74 in oligodendrocyte. Last, we profiled the bidirectional ligand-receptor interactions at the neighbor cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found GPR37L1_PSAP and GPR37_PSAP were top 2 enriched gene-pairs between microglia and fibroblast or microglia and astrocyte. Together, the establishment of these profiles firstly uncovered scar spatial heterogeneity and lineage trajectory, provide an unbiased view of scar and served as a valuable resource for CNS injury treatment.

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Know How to Regrow—Axon Regeneration in the Zebrafish Spinal Cord

Cells ◽

10.3390/cells10061404 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1404

Author(s):

Vasiliki Tsata ◽

Daniel Wehner

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Molecular Basis ◽

Axon Regeneration ◽

Target Cells ◽

Spinal Cord Regeneration ◽

Long Distance ◽

Extrinsic Factors ◽

Know How ◽

Cord Injury

The capacity for long-distance axon regeneration and functional recovery after spinal cord injury is poor in mammals but remarkable in some vertebrates, including fish and salamanders. The cellular and molecular basis of this interspecies difference is beginning to emerge. This includes the identification of target cells that react to the injury and the cues directing their pro-regenerative responses. Among existing models of successful spinal cord regeneration, the zebrafish is arguably the most understood at a mechanistic level to date. Here, we review the spinal cord injury paradigms used in zebrafish, and summarize the breadth of neuron-intrinsic and -extrinsic factors that have been identified to play pivotal roles in the ability of zebrafish to regenerate central nervous system axons and recover function.

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