scholarly journals Plasticity of the Injured Spinal Cord

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1886
Author(s):  
Nicolas Guérout
Keyword(s):  
Spinal Cord ◽  
Surgical Intervention ◽  
Symptomatic Relief ◽  
Glial Scar ◽  
Injured Spinal Cord ◽  
Sensory Deficits ◽  
Recovery Potential ◽  
Axonal Regrowth ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Complete spinal cord injury (SCI) leads to permanent motor, sensitive and sensory deficits. In humans, there is currently no therapy to promote recovery and the only available treatments include surgical intervention to prevent further damage and symptomatic relief of pain and infections in the acute and chronic phases, respectively. Basically, the spinal cord is classically viewed as a nonregenerative tissue with limited plasticity. Thereby the establishment of the “glial” scar which appears within the SCI is mainly described as a hermetic barrier for axon regeneration. However, recent discoveries have shed new light on the intrinsic functional plasticity and endogenous recovery potential of the spinal cord. In this review, we will address the different aspects that the spinal cord plasticity can take on. Indeed, different experimental paradigms have demonstrated that axonal regrowth can occur even after complete SCI. Moreover, recent articles have demonstrated too that the “glial” scar is in fact composed of several cellular populations and that each of them exerts specific roles after SCI. These recent discoveries underline the underestimation of the plasticity of the spinal cord at cellular and molecular levels. Finally, we will address the modulation of this endogenous spinal cord plasticity and the perspectives of future therapeutic opportunities which can be offered by modulating the injured spinal cord microenvironment.

scholarly journals Taurine promotes axonal regeneration after a complete spinal cord injury in lampreys

2019 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Blanca Fernández-López ◽  
Natividad Pereiro ◽  
Anunciación Lafuente ◽  
María Celina Rodicio ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Axon Regeneration ◽  
Traumatic Event ◽  
Axonal Regrowth ◽  
Cord Injury ◽  
Taurine Treatment ◽  
Complete Spinal Cord Injury ◽  
The Brain

AbstractTaurine is one of the most abundant free amino acids in the brain. It is well known that taurine protects the brain from further damage after a traumatic event. However, only a few ex vivo studies have looked at the possible role of taurine in the regulation of axon regeneration after injury. Here, we aimed to reveal the possible role for taurine in the modulation of axonal regeneration following a complete spinal cord injury (SCI) using lampreys as an animal model. The brainstem of lampreys contains several individually identifiable descending neurons that differ greatly in their capacity for axonal regeneration after SCI. This offers a convenient model to promote or inhibit axonal regrowth in the same in vivo preparation. First, we carried out high performance liquid chromatography experiments to measure taurine levels in the spinal cord following SCI. Our results revealed a statistically significant increase in taurine levels 4 weeks post lesion, which suggested that taurine might have a positive effect on axonal regrowth. Based on these results, we decided to apply an acute taurine treatment at the site of injury to study its effect on axon regeneration. Results from these experiments show that an acute taurine treatment enhances axonal regeneration following SCI in lampreys. This offers a novel way to try to promote axon regeneration after nervous system injuries in mammalian models.

scholarly journals Self-Assembling Peptide Nanofiber Scaffold Enhanced with RhoA Inhibitor CT04 Improves Axonal Regrowth in the Transected Spinal Cord

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Weiwei Zhang ◽  
Xiaoduo Zhan ◽  
Mingyong Gao ◽  
Audra D. Hamilton ◽  
Zhongying Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Axonal Regeneration ◽  
Therapeutic Potential ◽  
Injured Spinal Cord ◽  
Thoracic Spinal Cord ◽  
Nanofiber Scaffold ◽  
Self Assembling ◽  
Axonal Regrowth ◽  
Thoracic Spinal ◽  
Cord Injury

The present study was designed to explore the therapeutic potential of self-assembling peptide nanofiber scaffold (SAPNS) delivered RhoA inhibitor to ameliorate the hostile microenvironment of injured spinal cord for axonal regeneration. After a transection was applied to the thoracic spinal cord of mice, the combination of SAPNS and CT04 (a cell permeable RhoA inhibitor), single SAPNS with vehicle, or saline was transplanted into the lesion cavity. Results showed that SAPNS+CT04 implants achieved the best therapeutic outcomes among treatment groups. The novel combination not only reconstructed the injured nerve gap but also elicited significant axonal regeneration and motor functional recovery. Additionally, the combination also effectively reduced the apoptosis and infiltration of activated macrophages in the injured spinal cord. Collectively, the present study demonstrated that SAPNS-based delivery of RhoA inhibitor CT04 presented a highly potential therapeutic strategy for spinal cord injury with reknitting lesion gap, attenuating secondary injury, and improving axonal regrowth.

scholarly journals The Biology of Regeneration Failure and Success After Spinal Cord Injury

2018 ◽  
Vol 98 (2) ◽  
pp. 881-917 ◽  
Author(s):  
Amanda Phuong Tran ◽  
Philippa Mary Warren ◽  
Jerry Silver
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Axonal Regeneration ◽  
Molecular Mechanisms ◽  
Glial Scar ◽  
Perineuronal Net ◽  
Physical Trauma ◽  
Axonal Regrowth ◽  
Cord Injury

Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular and molecular mechanisms following SCI that compromise regeneration or neuroplasticity is needed to develop new strategies to promote axonal regrowth and restore function. Physical trauma to the spinal cord results in vascular disruption that, in turn, causes blood-spinal cord barrier rupture leading to hemorrhage and ischemia, followed by rampant local cell death. As subsequent edema and inflammation occur, neuronal and glial necrosis and apoptosis spread well beyond the initial site of impact, ultimately resolving into a cavity surrounded by glial/fibrotic scarring. The glial scar, which stabilizes the spread of secondary injury, also acts as a chronic, physical, and chemo-entrapping barrier that prevents axonal regeneration. Understanding the formative events in glial scarring helps guide strategies towards the development of potential therapies to enhance axon regeneration and functional recovery at both acute and chronic stages following SCI. This review will also discuss the perineuronal net and how chondroitin sulfate proteoglycans (CSPGs) deposited in both the glial scar and net impede axonal outgrowth at the level of the growth cone. We will end the review with a summary of current CSPG-targeting strategies that help to foster axonal regeneration, neuroplasticity/sprouting, and functional recovery following SCI.

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 Genes and miRNAs as Hurdles and Promoters of Corticospinal Tract Regeneration in Spinal Cord Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Marina Boido ◽  
Alessandro Vercelli
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Chronic Phase ◽  
Axon Growth ◽  
Glial Scar ◽  
Neural Regeneration ◽  
Axonal Regrowth ◽  
Cord Injury ◽  
Sensory Motor

Spinal cord injury (SCI) is a devastating lesion to the spinal cord, which determines the interruption of ascending/descending axonal tracts, the loss of supraspinal control of sensory-motor functions below the injured site, and severe autonomic dysfunctions, dramatically impacting the quality of life of the patients. After the acute inflammatory phase, the progressive formation of the astrocytic glial scar characterizes the acute-chronic phase: such scar represents one of the main obstacles to the axonal regeneration that, as known, is very limited in the central nervous system (CNS). Unfortunately, a cure for SCI is still lacking: the current clinical approaches are mainly based on early vertebral column stabilization, anti-inflammatory drug administration, and rehabilitation programs. However, new experimental therapeutic strategies are under investigation, one of which is to stimulate axonal regrowth and bypass the glial scar. One major issue in axonal regrowth consists of the different genetic programs, which characterize axonal development and maturation. Here, we will review the main hurdles that in adulthood limit axonal regeneration after SCI, describing the key genes, transcription factors, and miRNAs involved in these processes (seen their reciprocal influencing action), with particular attention to corticospinal motor neurons located in the sensory-motor cortex and subjected to axotomy in case of SCI. We will highlight the functional complexity of the neural regeneration programs. We will also discuss if specific axon growth programs, that undergo a physiological downregulation during CNS development, could be reactivated after a spinal cord trauma to sustain regrowth, representing a new potential therapeutic approach.

Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury

2010 ◽  
Vol 13 (2) ◽  
pp. 169-180 ◽  
Author(s):  
Rong Hu ◽  
Jianjun Zhou ◽  
Chunxia Luo ◽  
Jiangkai Lin ◽  
Xianrong Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mr Imaging ◽  
Rating Scale ◽  
Time Window ◽  
Critical Time ◽  
Glial Scar ◽  
Electrophysiological Recording ◽  
Axonal Regrowth ◽  
Cord Injury

Object A glial scar is thought to be responsible for halting neuroregeneration following spinal cord injury (SCI). However, little quantitative evidence has been provided to show the relationship of a glial scar and axonal regrowth after injury. Methods In this study performed in rats and dogs, a traumatic SCI model was made using a weight-drop injury device, and tissue sections were stained with H & E for immunohistochemical analysis. The function and behavior of model animals were tested using electrophysiological recording and the Basso-Beattie-Bresnahan Locomotor Rating Scale, respectively. The cavity in the spinal cord after SCI in dogs was observed using MR imaging. Results The morphological results showed that the formation of an astroglial scar was defined at 4 weeks after SCI. While regenerative axons reached the vicinity of the lesion site, the glial scar blocked the extension of regrown axons. In agreement with these findings, the electrophysiological, behavioral, and in vivo MR imaging tests showed that functional recovery reached a plateau at 4 weeks after SCI. The thickness of the glial scars in the injured rat spinal cords was also measured. The mean thickness of the glial scar rostral and caudal to the lesion cavity was 107.00 ± 20.12 μm; laterally it was 69.92 ± 15.12 μm. Conclusions These results provide comprehensive evidence indicating that the formation of a glial scar inhibits axonal regeneration at 4 weeks after SCI. This study reveals a critical time window of postinjury recovery and a detailed spatial orientation of glial scar, which would provide an important basis for the development of therapeutic strategy for glial scar ablation.

Neurological Recovery in Traumatic Spinal Cord Injury Patient with Delayed Surgical Intervention

2018 ◽  
Vol 1 (2) ◽  
pp. 34
Author(s):  
Mochamad Targib Alatas
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Surgical Intervention ◽  
Case Series ◽  
Spinal Cord Injury Patient ◽  
Traumatic Spinal Cord Injury ◽  
Best Interest ◽  
Score Improvement ◽  
Cord Injury ◽  
Injury Patient

Early surgical treatment for traumatic spinal cord injury (SCI) patients has been proven to yield better improvement on neurological state, and widely practiced among surgeons in this field. However, it is not always affordable in every clinical setting. It is undeniable that surgery for chronic SCI has more challenges as the malunion of vertebral bones might have initiated, thus requires more complex operating techniques. In this case series, we report 7 patients with traumatic SCI whose surgical intervention is delayed due to several reasons. Initial motoric scores vary from 0 to 3, all have their interval periods supervised between outpatient clinic visits. On follow up they demonstrate significant neurological development defined by at least 2 grades motoric score improvement. Physical rehabilitation also began before surgery was conducted. These results should encourage surgeons to keep striving for the patient’s best interest, even when the injury has taken place weeks or even months before surgery is feasible because clinical improvement for these patients is not impossible. 

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