scholarly journals Extrinsic and Intrinsic Regulation of Axon Regeneration by MicroRNAs after Spinal Cord Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ping Li ◽  
Zhao-Qian Teng ◽  
Chang-Mei Liu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Axon Regeneration ◽  
Therapeutic Potential ◽  
Glial Scar ◽  
Scar Formation ◽  
Extrinsic Factors ◽  
Cord Injury ◽  
The Central Nervous System

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.

scholarly journals Importance of the vasculature in cyst formation after spinal cord injury

2009 ◽  
Vol 11 (4) ◽  
pp. 432-437 ◽  
Author(s):  
Gemma E. Rooney ◽  
Toshiki Endo ◽  
Syed Ameenuddin ◽  
Bingkun Chen ◽  
Sandeep Vaishya ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Cyst Formation ◽  
Glial Scar ◽  
Scar Formation ◽  
Cystic Formation ◽  
Dural Closure ◽  
Surgical Methods ◽  
Cord Injury

Object Glial scar and cystic formation greatly contribute to the inhibition of axonal regeneration after spinal cord injury (SCI). Attempts to promote axonal regeneration are extremely challenging in this type of hostile environment. The objective of this study was to examine the surgical methods that may be used to assess the factors that influence the level of scar and cystic formation in SCI. Methods In the first part of this study, a complete transection was performed at vertebral level T9–10 in adult female Sprague-Dawley rats. The dura mater was either left open (control group) or was closed using sutures or hyaluronic acid. In the second part of the study, complete or subpial transection was performed, with the same dural closure technique applied to both groups. Histological analysis of longitudinal sections of the spinal cord was performed, and the percentage of scar and cyst formation was determined. Results Dural closure using sutures resulted in significantly less glial scar formation (p = 0.0248), while incorporation of the subpial transection surgical technique was then shown to significantly decrease cyst formation (p < 0.0001). Conclusions In this study, the authors demonstrated the importance of the vasculature in cyst formation after spinal cord trauma and confirmed the importance of dural closure in reducing glial scar formation.

Schwann cell transplantation for spinal cord injury repair: its significant therapeutic potential and prospectus

2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Haruo Kanno ◽  
Damien D. Pearse ◽  
Hiroshi Ozawa ◽  
Eiji Itoi ◽  
Mary Bartlett Bunge
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Axonal Regeneration ◽  
Therapeutic Strategy ◽  
Glial Scar ◽  
Scar Formation ◽  
Tissue Loss ◽  
Injured Spinal Cord ◽  
Cord Injury

AbstractTransplantation of Schwann cells (SCs) is a promising therapeutic strategy for spinal cord repair. The introduction of SCs into the injured spinal cord has been shown to reduce tissue loss, promote axonal regeneration, and facilitate myelination of axons for improved sensorimotor function. The pathology of spinal cord injury (SCI) comprises multiple processes characterized by extensive cell death, development of a milieu inhibitory to growth, and glial scar formation, which together limits axonal regeneration. Many studies have suggested that significant functional recovery following SCI will not be possible with a single therapeutic strategy. The use of additional approaches with SC transplantation may be needed for successful axonal regeneration and sufficient functional recovery after SCI. An example of such a combination strategy with SC transplantation has been the complementary administration of neuroprotective agents/growth factors, which improves the effect of SCs after SCI. Suspension of SCs in bioactive matrices can also enhance transplanted SC survival and increase their capacity for supporting axonal regeneration in the injured spinal cord. Inhibition of glial scar formation produces a more permissive interface between the SC transplant and host spinal cord for axonal growth. Co-transplantation of SCs and other types of cells such as olfactory ensheathing cells, bone marrow mesenchymal stromal cells, and neural stem cells can be a more effective therapy than transplantation of SCs alone following SCI. This article reviews some of the evidence supporting the combination of SC transplantation with additional strategies for SCI repair and presents a prospectus for achieving better outcomes for persons with SCI.

scholarly journals SiRNA in MSCs-Derived Exosomes Silences Ctgf Gene for Corticospinal Axon Regeneration and Locomotor Recovery in Spinal Cord Injury Rats

2019 ◽  
Author(s):  
Wei Huang ◽  
Mingjia Qu ◽  
Lu Li ◽  
Tao Liu ◽  
Ruimeng Duan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Axon Regeneration ◽  
Drug Loading ◽  
Glial Scar ◽  
Tissue Growth ◽  
Scar Formation ◽  
Cord Injury

Abstract As RNA interference (RNAi) received solicitous attention by many for its promising performance in gene therapy recently, and how to obtain a choice small interfering RNA (siRNA) vector has become a moot point at this moment. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency and easy penetration across the blood-brain/spinal cord barrier, renowned as excellent carriers of bioactive substances. Previous studies have confirmed the detrimental effect of connective tissue growth factor (CTGF) on axonal regeneration after spinal cord injury (SCI) via stimulating the unrestricted growth of glial scars. In this study, we applied mesenchymal stem cells (MSCs)-derived Exo as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosome-siRNA (Exo-siRNA) that could specifically silence Ctgf gene in the injury sites by electroporation.During the administration, we injected Exo-siRNAs into the tail vein of SCI rats, and their distribution and accumulation in the spinal cord were visualized by in vivo fluorescence imaging. Relevant in vivo and in vitro experiments in this study showed that Exo-siRNA not only effectively inhibited the expressions of Ctgf gene and glial scar formation related proteins, such as GFAP, vimentin fibronectin and laminin, in the injured spinal cord segments, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly up-regulated several neurotrophic factors and anti-inflammatory factors (e.g., TGF-β1), acting as a facilitator of axon regeneration of nerve-injured motor neurons. Thus, the motor function of SCI rats were remarkably promoted.In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

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

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.

SiRNA in MSCs-Derived Exosomes Silences Ctgf Gene for Corticospinal Axon Regeneration and Locomotor Recovery in Spinal Cord Injury Rats

2020 ◽  
Author(s):  
Wei Huang ◽  
Mingjia Qu ◽  
Lu Li ◽  
Tao Liu ◽  
Ruimeng Duan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Axon Regeneration ◽  
Drug Loading ◽  
Glial Scar ◽  
Tissue Growth ◽  
Scar Formation ◽  
Cord Injury

Abstract As RNA interference (RNAi) received solicitous attention by many for its promising performance in gene therapy recently, and how to obtain a choice small interfering RNA (siRNA) vector has become a moot point at this moment. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency and easy penetration across the blood-brain/spinal cord barrier, renowned as excellent carriers of bioactive substances. Previous studies have confirmed the detrimental effect of connective tissue growth factor (CTGF) on axonal regeneration after spinal cord injury (SCI) via stimulating the unrestricted growth of glial scars. In this study, we applied mesenchymal stem cells (MSCs)-derived Exo as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosome-siRNA (Exo-siRNA) that could specifically silence Ctgf gene in the injury sites by electroporation. During the administration, we injected Exo-siRNAs into the tail vein of SCI rats, and their distribution and accumulation in the spinal cord were visualized by in vivo fluorescence imaging. Relevant in vivo and in vitro experiments in this study showed that Exo-siRNA not only effectively inhibited the expressions of Ctgf gene and glial scar formation related proteins, such as GFAP, vimentin fibronectin and laminin, in the injured spinal cord segments, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly up-regulated several neurotrophic factors and anti-inflammatory factors (e.g., TGF-β1), acting as a facilitator of axon regeneration of nerve-injured motor neurons. Thus, the motor function of SCI rats were remarkably promoted. In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

scholarly journals Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury

RSC Advances ◽  
2020 ◽  
Vol 10 (32) ◽  
pp. 18677-18686
Author(s):  
Jia Liu ◽  
Kai Li ◽  
Ke Huang ◽  
Chengliang Yang ◽  
Zhipeng Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Traumatic Injury ◽  
High Rate ◽  
Plga Microspheres ◽  
Cord Injury ◽  
The Central Nervous System

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery.

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