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Special Issue "Combined Treatments and Therapies to Cure Spinal Cord Injury"

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 15 November 2023 | Viewed by 7474

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Special Issue Editor

Dr. Nicolas Guerout

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Guest Editor

SPPIN - Saints-Pères Paris Institute for the Neurosciences - CNRS UMR 8003, Université Paris Cité, F-75006 Paris, France
Interests: spinal cord injury; cellular transplantation; magnetic stimulation; spinal scar; non-invasive treatment; axonal regrowth; functional recovery; tissue repair

Special Issue Information

Dear Colleagues,

Spinal cord injury (SCI) is a rare disease of the central nervous system (CNS), most often originating from trauma following road accidents, falls or violence, causing the loss of motor, sensory and autonomic functions. To date, there is no curative treatment that can be offered to injured patients. The initial trauma induces tissue destruction, the rupture of blood vessels and axons and death of neurons and oligodendrocytes at the site of injury, these events leading to myelin release and inflammation. This reactionary cascade leads to the formation of a spinal scar composed of astrocytes, microglial cells and macrophages, fibroblasts and cystic cavities. This scar has a dual role: beneficial in delimiting the lesioned area, and deleterious in preventing axonal regrowth; thus, leading to a loss of connection between the CNS and the periphery. Many treatments have been tested to allow tissue and functional recovery after SCI. However, the complexity of the injury suggests that a single treatment is not sufficient to induce real benefits in humans. Therefore, it is thought that only the use of combination therapies would be effective in promoting recovery after SCI, although the ideal combination remains to be determined.

We cordially invite you to contribute to the Special Issue entitled “Combined Treatments and Therapies to Cure Spinal Cord Injury”. Our aim is to provide most relevant information concerning innovative treatment modalities and their combinations as potential innovative treatments after SCI. Original investigations and review articles are both welcome.

Dr. Nicolas Guerout
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

spinal cord injury
tissue repair
functional recovery
combined treatments
innovative therapy
glial scar
inflammation
axonal regrowth

Published Papers (7 papers)

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Research

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Open AccessArticle

Human Adipose-Derived Stem Cells Reduce Cellular Damage after Experimental Spinal Cord Injury in Rats

Emiliano Neves Vialle

Letícia Fracaro

Fabiane Barchiki

Alejandro Correa Dominguez

André de Oliveira Arruda

Marcia Olandoski

Paulo Roberto Slud Brofman

and

Carmen Lúcia Kuniyoshi Rebelatto

Biomedicines 2023, 11(5), 1394; https://doi.org/10.3390/biomedicines11051394 - 08 May 2023

Viewed by 547

Abstract

Traumatic spinal cord injury (SCI) is a devastating condition without an effective therapy. Cellular therapies are among the promising treatment strategies. Adult stem cells, such as mesenchymal stem cells, are often used clinical research for their immunomodulatory and regenerative potential. This study aimed to evaluate the effect of human adipose tissue-derived stem cells (ADSC) infusion through the cauda equina in rats with SCI. The human ADSC from bariatric surgery was isolated, expanded, and characterized. Wistar rats were subjected to blunt SCI and were divided into four groups. Two experimental groups (EG): EG1 received one ADSC infusion after SCI, and EG2 received two infusions, the first one after SCI and the second infusion seven days after the injury. Control groups (CG1 and CG2) received infusion with a culture medium. In vivo, cell tracking was performed 48 h and seven days after ADSC infusion. The animals were followed up for 40 days after SCI, and immunohistochemical quantification of myelin, neurons, and astrocytes was performed. Cellular tracking showed cell migration towards the injury site. ADSC infusion significantly reduced neuronal loss, although it did not prevent the myelin loss or enhance the area occupied by astrocytes compared to the control group. The results were similar when comparing one or two cell infusions. The injection of ADSC distal to the injured area was shown to be a safe and effective method for cellular administration in spinal cord injury. Full article

(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)

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Open AccessArticle

Microneurotrophin BNN27 Reduces Astrogliosis and Increases Density of Neurons and Implanted Neural Stem Cell-Derived Cells after Spinal Cord Injury

Konstantina Georgelou

Erasmia-Angeliki Saridaki

Kanelina Karali

Argyri Papagiannaki

Ioannis Charalampopoulos

Achille Gravanis

and

Dimitrios S. Tzeranis

Biomedicines 2023, 11(4), 1170; https://doi.org/10.3390/biomedicines11041170 - 13 Apr 2023

Viewed by 846

Abstract

Microneurotrophins, small-molecule mimetics of endogenous neurotrophins, have demonstrated significant therapeutic effects on various animal models of neurological diseases. Nevertheless, their effects on central nervous system injuries remain unknown. Herein, we evaluate the effects of microneurotrophin BNN27, an NGF analog, in the mouse dorsal column crush spinal cord injury (SCI) model. BNN27 was delivered systemically either by itself or combined with neural stem cell (NSC)-seeded collagen-based scaffold grafts, demonstrated recently to improve locomotion performance in the same SCI model. Data validate the ability of NSC-seeded grafts to enhance locomotion recovery, neuronal cell integration with surrounding tissues, axonal elongation and angiogenesis. Our findings also show that systemic administration of BNN27 significantly reduced astrogliosis and increased neuron density in mice SCI lesion sites at 12 weeks post injury. Furthermore, when BNN27 administration was combined with NSC-seeded PCS grafts, BNN27 increased the density of survived implanted NSC-derived cells, possibly addressing a major challenge of NSC-based SCI treatments. In conclusion, this study provides evidence that small-molecule mimetics of endogenous neurotrophins can contribute to effective combinatorial treatments for SCI, by simultaneously regulating key events of SCI and supporting grafted cell therapies in the lesion site. Full article

(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)

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Open AccessArticle

The Role of Transcranial Magnetic Stimulation, Peripheral Electrotherapy, and Neurophysiology Tests for Managing Incomplete Spinal Cord Injury

Katarzyna Leszczyńska

and

Juliusz Huber

Biomedicines 2023, 11(4), 1035; https://doi.org/10.3390/biomedicines11041035 - 27 Mar 2023

Viewed by 668

Abstract

Efforts to find therapeutic methods that support spinal cord functional regeneration continue to be desirable. Natural recovery is limited, so high hopes are being placed on neuromodulation methods which promote neuroplasticity, such as repetitive transcranial magnetic stimulation (rTMS) and electrical stimulation used as treatment options for managing incomplete spinal cord injury (iSCI) apart from kinesiotherapy. However, there is still no agreement on the methodology and algorithms for treatment with these methods. The search for effective therapy is also hampered by the use of different, often subjective in nature, evaluation methods and difficulties in assessing the actual results of the therapy versus the phenomenon of spontaneous spinal cord regeneration. In this study, an analysis was performed on the database of five trials, and the cumulative data are presented. Participants (iSCI patients) were divided into five groups on the basis of the treatment they had received: rTMS and kinesiotherapy (N = 36), peripheral electrotherapy and kinesiotherapy (N = 65), kinesiotherapy alone (N = 55), rTMS only (N = 34), and peripheral electrotherapy mainly (N = 53). We present changes in amplitudes and frequencies of the motor units’ action potentials recorded by surface electromyography (sEMG) from the tibialis anterior—the index muscle for the lower extremity and the percentage of improvement in sEMG results before and after the applied therapies. The increase in values in sEMG parameters represents the better ability of motor units to recruit and, thus, improvement of neural efferent transmission. Our results indicate that peripheral electrotherapy provides a higher percentage of neurophysiological improvement than rTMS; however, the use of any of these additional stimulation methods (rTMS or peripheral electrotherapy) provided better results than the use of kinesiotherapy alone. The best improvement of tibialis anterior motor units’ activity in iSCI patients provided the application of electrotherapy conjoined with kinesiotherapy and rTMS conjoined with kinesiotherapy. We also undertook a review of the current literature to identify and summarise available works which address the use of rTMS or peripheral electrotherapy as neuromodulation treatment options in patients after iSCI. Our goal is to encourage other clinicians to implement both types of stimulation into the neurorehabilitation program for subjects after iSCI and evaluate their effectiveness with neurophysiological tests such as sEMG so further results and algorithms can be compared across studies. Facilitating the motor rehabilitation process by combining two rehabilitation procedures together was confirmed. Full article

(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)

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Open AccessArticle

Combined Transcutaneous Electrical Spinal Cord Stimulation and Task-Specific Rehabilitation Improves Trunk and Sitting Functions in People with Chronic Tetraplegia

and

Biomedicines 2023, 11(1), 34; https://doi.org/10.3390/biomedicines11010034 - 23 Dec 2022

Cited by 2 | Viewed by 1210

Abstract

The aim of this study was to examine the effects of transcutaneous electrical spinal cord stimulation (TSCS) and conventional task-specific rehabilitation (TSR) on trunk control and sitting stability in people with chronic tetraplegia secondary to a spinal cord injury (SCI). Five individuals with complete cervical (C4–C7) cord injury participated in 24-week therapy that combined TSCS and TSR in the first 12 weeks, followed by TSR alone for another 12 weeks. The TSCS was delivered simultaneously at T11 and L1 spinal levels, at a frequency ranging from 20–30 Hz with 0.1–1.0 ms. pulse width biphasically. Although the neurological prognosis did not manifest after either treatment, the results show that there were significant increases in forward reach distance (10.3 ± 4.5 cm), right lateral reach distance (3.7 ± 1.8 cm), and left lateral reach distance (3.0 ± 0.9 cm) after the combinational treatment (TSCS+TSR). The stimulation also significantly improved the participants’ trunk control and function in sitting. Additionally, the trunk range of motion and the electromyographic response of the trunk muscles were significantly elevated after TSCS+TSR. The TSCS+TSR intervention improved independent trunk control with significantly increased static and dynamic sitting balance, which were maintained throughout the TSR period and the follow-up period, indicating long-term sustainable recovery. Full article

(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)

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Review

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Open AccessReview

Differentiating Lumbar Spinal Etiology from Peripheral Plexopathies

and

Biomedicines 2023, 11(3), 756; https://doi.org/10.3390/biomedicines11030756 - 02 Mar 2023

Viewed by 1266

Abstract

Clinicians have managed and treated lower back pain since the earliest days of practice. Historically, lower back pain and its accompanying symptoms of radiating leg pain and muscle weakness have been recognized to be due to any of the various lumbar spine pathologies that lead to the compression of the lumbar nerves at the root, the most common of which is the radiculopathy known as sciatica. More recently, however, with the increased rise in chronic diseases, the importance of differentially diagnosing a similarly presenting pathology, known as lumbosacral plexopathy, cannot be understated. Given the similar clinical presentation of lumbar spine pathologies and lumbosacral plexopathies, it can be difficult to differentiate these two diagnoses in the clinical setting. Resultingly, the inappropriate diagnosis of either pathology can result in ineffective clinical management. Thus, this review aims to aid in the clinical differentiation between lumbar spine pathology and lumbosacral plexopathy. Specifically, this paper delves into spine and plexus anatomy, delineates the clinical assessment of both pathologies, and highlights powerful diagnostic tools in the hopes of bolstering appropriate diagnosis and treatment. Lastly, this review will describe emerging treatment options for both pathologies in the preclinical and clinical realms, with a special emphasis on regenerative nerve therapies. Full article

(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)

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Open AccessReview

Evidence of Improvement of Lower Limb Functioning Using Hydrotherapy on Spinal Cord Injury Patients

Liliana Elena Stanciu

Madalina Gabriela Iliescu

Liliana Vlădăreanu

Alexandra Ecaterina Ciota

Elena-Valentina Ionescu

and

Claudia Ileana Mihailov

Biomedicines 2023, 11(2), 302; https://doi.org/10.3390/biomedicines11020302 - 21 Jan 2023

Viewed by 1180

Abstract

Background: Spinal cord injury (SCI) is a devastating problem for modern society, whether it affects young people in the most productive period of their lives or the elderly. The spinal cord injury is currently without curative treatment and the therapeutic intervention aims to minimize secondary complications and maximize residual function through rehabilitation medicine. The main objective of this scientific paper is to determine whether there is evidence in the literature regarding the importance and/or use of hydrotherapy, as part of the therapeutic management of the SCI patient, in order to decrease the degree of spasticity, of pain symptoms, increase or maintain range of motion, improve respiratory, cardiovascular, and metabolic status, as well as improve function and psychological benefits. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedures, the following databases were analyzed between 2000 and 2021: Pub Med, Pub Med Central, Science Direct, Scopus, and SpringerLink. Initial keywords: rehabilitation treatment, spinal cord injury. Additional keywords: hydrotherapy, aqua therapy, spasticity, human. For the scientific quality of the included articles, risk of bias was assessed using the Downs and Black Appraisal Modified Scale. Results: Our research used only four publications as per PRISMA protocol, assessed with Downs and Black Scale. The study models used in the individual studies included in the research are the following: two systematic reviews, one experimental non-randomized control, and one individual semi-structured interview. Due to the low number of studies, despite two of them being reviews, there is the necessity for a more standardized methodology to prove the benefits hydrotherapy for SCI patients for the improvement of lower limb functioning. Conclusion: Hydrotherapy is an important component of the treatment of an SCI patient, despite the limited number of scientific studies that support this aspect. Clinical trials in the future are required. Full article

(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)

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Open AccessReview

Designing a Clinical Trial with Olfactory Ensheathing Cell Transplantation-Based Therapy for Spinal Cord Injury: A Position Paper

and

Biomedicines 2022, 10(12), 3153; https://doi.org/10.3390/biomedicines10123153 - 06 Dec 2022

Viewed by 941

Abstract

Spinal cord injury (SCI) represents an urgent unmet need for clinical reparative therapy due to its largely irreversible and devastating effects on patients, and the tremendous socioeconomic burden to the community. While different approaches are being explored, therapy to restore the lost function remains unavailable. Olfactory ensheathing cell (OEC) transplantation is a promising approach in terms of feasibility, safety, and limited efficacy; however, high variability in reported clinical outcomes prevent its translation despite several clinical trials. The aims of this position paper are to present an in-depth analysis of previous OEC transplantation-based clinical trials, identify existing challenges and gaps, and finally propose strategies to improve standardization of OEC therapies. We have reviewed the study design and protocols of clinical trials using OEC transplantation for SCI repair to investigate how and why the outcomes show variability. With this knowledge and our experience as a team of biologists and clinicians with active experience in the field of OEC research, we provide recommendations regarding cell source, cell purity and characterisation, transplantation dosage and format, and rehabilitation. Ultimately, this position paper is intended to serve as a roadmap to design an effective clinical trial with OEC transplantation-based therapy for SCI repair. Full article

(This article belongs to the Special Issue Combined Treatments and Therapies to Cure Spinal Cord Injury)

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