scholarly journals Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon

2008 ◽  
Vol 25 (5) ◽  
pp. E2 ◽  
Author(s):  
James W. Rowland ◽  
Gregory W. J. Hawryluk ◽  
Brian Kwon ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Apoptotic Cell ◽  
Vascular Dysfunction ◽  
Mechanical Injury ◽  
Current Status ◽  
Emerging Therapies ◽  
Cord Injury ◽  
Central Myelin ◽  
Do So

This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho–associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

scholarly journals Treatment of spinal cord injury with mesenchymal stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Ling Liau ◽  
Qi Hao Looi ◽  
Wui Chuen Chia ◽  
Thayaalini Subramaniam ◽  
Min Hwei Ng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Poor Quality ◽  
Nerve Tissue ◽  
Current Status ◽  
Therapeutic Effects ◽  
Biological Therapies ◽  
Loss Of Function ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life. Results This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue. Conclusion These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

Recurrent autonomic dysreflexia exacerbates vascular dysfunction after spinal cord injury

2010 ◽  
Vol 10 (12) ◽  
pp. 1108-1117 ◽  
Author(s):  
Nima Alan ◽  
Leanne M. Ramer ◽  
Jessica A. Inskip ◽  
Saeid Golbidi ◽  
Matt S. Ramer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Vascular Dysfunction ◽  
Autonomic Dysreflexia ◽  
Cord Injury

scholarly journals Transcriptomic Screening of Microvascular Endothelial Cells Implicates Novel Molecular Regulators of Vascular Dysfunction after Spinal Cord Injury

2008 ◽  
Vol 28 (11) ◽  
pp. 1771-1785 ◽  
Author(s):  
Richard L Benton ◽  
Melissa A Maddie ◽  
Christopher A Worth ◽  
Edward T Mahoney ◽  
Theo Hagg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Vascular Dysfunction ◽  
Fluorescein Isothiocyanate ◽  
Microvascular Dysfunction ◽  
Cell Counting ◽  
Protein Levels ◽  
Cord Injury ◽  
Biochemical Analyses ◽  
High Degree

Microvascular dysfunction is a critical pathology that underlies the evolution of secondary injury mechanisms after traumatic spinal cord injury (SCI). However, little is known of the molecular regulation of endothelial cell (EC) plasticity observed acutely after injury. One reason for this is the relative lack of methods to quickly and efficiently obtain highly enriched spinal microvascular ECs for high-throughput molecular and biochemical analyses. Adult C57BI/6 mice received an intravenous injection of fluorescein isothiocyanate (FITC)-conjugated Lycopersicon esculentum lectin, and FITC-lectin bound spinal microvessels were greatly enriched by fluorescence-activated cell sorter (FACS) purification. This technique allows for rapid (< 1.5 h postmortem) isolation of spinal cord microvascular ECs (smvECs). The results from cell counting, reverse-transcription polymerase chain reaction (RT-PCR), and western blot analyses show a high degree of EC enrichment at mRNA and protein levels. Furthermore, a focused EC biology microarray analysis identified multiple mRNAs dramatically increased in the EC compartment 24 h after SCI, which is a time point associated with the pathologic loss of spinal vasculature. These included thrombospondin-1, CCL5/RANTES, and urokinase plasminogen activator, suggesting they may represent targets for therapeutic intervention. Furthermore, these novel methodologic approaches will likely facilitate the discovery of molecular regulators of endothelial dysfunction in a variety of central nervous system (CNS) disorders including stroke and other neurodegenerative diseases having a vascular component.

scholarly journals Regenerative medicine for spinal cord injury: Current status and open issues

2009 ◽  
Vol 29 (3) ◽  
pp. 198-203 ◽  
Author(s):  
Masaya Nakamura ◽  
Narihito Nagoshi ◽  
Kanehiro Fujiyoshi ◽  
Shinjiro Kaneko ◽  
Yoshiaki Toyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Regenerative Medicine ◽  
Current Status ◽  
Cord Injury ◽  
Open Issues

scholarly journals The Impact of Compression Duration on the RhoA, P75, S100 Expression in Spinal Cord Injury in Rat

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Soheila Pourkhodadad ◽  
Zahra Hasannejad ◽  
Masoumeh Firouzi ◽  
Shayan Abdollahzadegan ◽  
Alexander R Vaccaro ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Apoptotic Cell ◽  
Neurotrophin Receptor ◽  
Spinal Cord Injury Model ◽  
Injury Model ◽  
Cord Injury ◽  
Secondary Injuries ◽  
The Difference ◽  
The Impact

Background: Compression of the spinal cord induces alterations in protein expression of neurons and glia cells, which in turn triggers a cascade of pathophysiologic events. It's well-documented that activation of inhibitory proteins following spinal cord injury stimulates activation of the RhoA via neurotrophin receptor p75 (p75NTR), which causes promotion of apoptotic cell death and inhibiting axon outgrowth. Elucidating the underlying factors driving the expressions during sustained compression is important to develop new therapeutic strategies. Objectives: To investigate the impact of compression duration on the RhoA, P75, and S100 expression in spinal cord injury model in rats. Methods: We investigated the impact of compression duration on the expression of RhoA, p75NTR, and S100β in rats with spinal cord injury (SCI). Initially, rats were subjected to SCI using an aneurism clip at the T9 vertebrae lamina for 3 sec or 10 min. Sham group was subjected to laminectomy only. We compared spinal cord histopathology at 3 and 14 days after injury for both short and prolonged compressive surgery groups. At the respective scarify times points, the rats were sacrificed, and the pathology of the injury was studied using light microscopy and immunohistochemistry. Results: We found a greater expression level of p75NTR, S100β, and RhoA in the prolonged compression group compared to the short compression group. The difference was statistically significant, indicating that earlier decompression can prevent the progress of secondary injuries due to higher expression levels of p75NTR, S100, and RhoA. Conclusions: This study demonstrated that early decompression of the spinal cord through the changes in p75NTR, S100β, and RhoA expression may modulate secondary injury events. Besides, it was found that using different inhibitors, especially for RhoA, might improve SCI-induced regeneration.

scholarly journals Changes in Expression of Receptor-Interacting Protein Kinase 1 in Secondary Neural Tissue Damage Following Spinal Cord Injury

2020 ◽  
Vol 15 ◽  
pp. 263310552090640
Author(s):  
Haruo Kanno ◽  
Hiroshi Ozawa ◽  
Kyoichi Handa ◽  
Taishi Murakami ◽  
Eiji Itoi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Tissue Damage ◽  
Time Course ◽  
Apoptotic Cell ◽  
Neural Tissue ◽  
Apoptotic Cell Death ◽  
Neural Cells ◽  
Cord Injury

Introduction: Necroptosis is a form of programmed cell death that is different from apoptotic cell death. Receptor-interacting protein kinase 1 (RIPK1) plays a particularly important function in necroptosis execution. This study investigated changes in expression of RIPK1 in secondary neural tissue damage following spinal cord injury in mice. The time course of the RIPK1 expression was also compared with that of apoptotic cell death in the lesion site. Methods and Materials: Immunostaining for RIPK1 was performed at different time points after spinal cord injury. The protein expressions of RIPK1 were determined by western blot. The RIPK1 expressions in various neural cells were investigated using immunohistochemistry. To investigate the time course of apoptotic cell death, TUNEL-positive cells were counted at the different time points. To compare the incidence of necroptosis and apoptosis, the RIPK1-labeled sections were co-stained with TUNEL. Results: The RIPK1 expression was significantly upregulated in the injured spinal cord. The upregulation of RIPK1 expression was observed in neurons, astrocytes, and oligodendrocytes. The increase in RIPK1 expression started at 4 hours and peaked at 3 days after injury. Time course of the RIPK1 expression was similar to that of apoptosis detected by TUNEL. Interestingly, the increased expression of RIPK1 was rarely observed in the TUNEL-positive cells. Furthermore, the number of RIPK1-positive cells was significantly higher than that of TUNEL-positive cells. Conclusions: This study demonstrated that the expression of RIPK1 increased in various neural cells and peaked at 3 days following spinal cord injury. The temporal change of the RIPK1 expression was analogous to that of apoptosis at the lesion site. However, the increase in RIPK1 expression was barely seen in the apoptotic cells. These findings suggested that the RIPK1 might contribute to the pathological mechanism of the secondary neural tissue damage after spinal cord injury.

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