Research

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Open AccessArticle

Comparative Analysis of Cytokine Profiles in Cerebrospinal Fluid and Blood Serum in Patients with Acute and Subacute Spinal Cord Injury

by Davran Sabirov, Sergei Ogurcov, Ilya Shulman, Ilyas Kabdesh, Ekaterina Garanina, Albert Sufianov, Albert Rizvanov and Yana Mukhamedshina

Biomedicines 2023, 11(10), 2641; https://doi.org/10.3390/biomedicines11102641 - 26 Sep 2023

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Abstract

Background: Cytokines are actively involved in the regulation of the inflammatory and immune responses and have crucial importance in the outcome of spinal cord injuries (SCIs). Examining more objective and representative indicators of the patient’s condition is still required to reveal the fundamental [...] Read more.

Background: Cytokines are actively involved in the regulation of the inflammatory and immune responses and have crucial importance in the outcome of spinal cord injuries (SCIs). Examining more objective and representative indicators of the patient’s condition is still required to reveal the fundamental patterns of the abovementioned posttraumatic processes, including the identification of changes in the expression of cytokines. Methods: We performed a dynamic (3, 7, and 14 days post-injury (dpi)) extended multiplex analysis of cytokine profiles in both CSF and blood serum of SCI patients with baseline American Spinal Injury Association Impairment Scale grades of A. Results: The data obtained showed a large elevation of IL6 (>58 fold) in CSF and IFN-γ (>14 fold) in blood serum at 3 dpi with a downward trend as the post-traumatic period increases. The level of cytokine CCL26 was significantly elevated in both CSF and blood serum at 3 days post-SCI, while other cytokines did not show the same trend in the different biosamples. Conclusions: The dynamic changes in cytokine levels observed in our study can explore the relationships with the SCI region and injury severity, paving the way for a better understanding of the pathophysiology of SCI and potentially more targeted and personalized therapeutic interventions. Full article

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

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13 pages, 1341 KiB

Open AccessArticle

Transcutaneous Spinal Cord Stimulation Improves Respiratory Muscle Strength and Function in Subjects with Cervical Spinal Cord Injury: Original Research

by Hatice Kumru, Loreto García-Alén, Aina Ros-Alsina, Sergiu Albu, Margarita Valles and Joan Vidal

Biomedicines 2023, 11(8), 2121; https://doi.org/10.3390/biomedicines11082121 - 27 Jul 2023

Cited by 1 | Viewed by 1210

Abstract

(1) Background: Respiratory muscle weakness is common following cervical spinal cord injury (cSCI). Transcutaneous spinal cord stimulation (tSCS) promotes the motor recovery of the upper and lower limbs. tSCS improved breathing and coughing abilities in one subject with tetraplegia. Objective: We therefore hypothesized [...] Read more.

(1) Background: Respiratory muscle weakness is common following cervical spinal cord injury (cSCI). Transcutaneous spinal cord stimulation (tSCS) promotes the motor recovery of the upper and lower limbs. tSCS improved breathing and coughing abilities in one subject with tetraplegia. Objective: We therefore hypothesized that tSCS applied at the cervical and thoracic levels could improve respiratory function in cSCI subjects; (2) Methods: This study was a randomized controlled trial. Eleven cSCI subjects received inspiratory muscle training (IMT) alone. Eleven cSCI subjects received tSCS combined with IMT (six of these subjects underwent IMT alone first and then they were given the opportunity to receive tSCS + IMT). The subjects evaluated their sensation of breathlessness/dyspnea and hypophonia compared to pre-SCI using a numerical rating scale. The thoracic muscle strength was assessed by maximum inspiratory (MIP), expiratory pressure (MEP), and spirometric measures. All assessments were conducted at baseline and after the last session. tSCS was applied at C3-4 and Th9-10 at a frequency of 30 Hz for 30 min on 5 consecutive days; (3) Results: Following tSCS + IMT, the subjects reported a significant improvement in breathlessness/dyspnea and hypophonia (p < 0.05). There was also a significant improvement in MIP, MEP, and forced vital capacity (p < 0.05). Following IMT alone, there were no significant changes in any measurement; (4) Conclusions: Current evidence supports the potential of tSCS as an adjunctive therapy to accelerate and enhance the rehabilitation process for respiratory impairments following SCI. However, further research is needed to validate these results and establish the long-term benefits of tSCS in this population. Full article

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

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14 pages, 3243 KiB

Open AccessArticle

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

by 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

Cited by 4 | Viewed by 1508

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 [...] Read more.

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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19 pages, 8952 KiB

Open AccessArticle

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

by 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

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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 [...] Read more.

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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18 pages, 958 KiB

Open AccessArticle

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

by Katarzyna Leszczyńska and Juliusz Huber

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

Cited by 3 | Viewed by 2214

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 [...] Read more.

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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18 pages, 2101 KiB

Open AccessArticle

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

by Niraj Singh Tharu, Monzurul Alam, Yan To Ling, Arnold YL Wong and Yong-Ping Zheng

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

Cited by 9 | Viewed by 2220

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 [...] Read more.

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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17 pages, 1974 KiB

Open AccessReview

Advancements in Spinal Cord Injury Repair: Insights from Dental-Derived Stem Cells

by Xueying Wen, Wenkai Jiang, Xiaolin Li, Qian Liu, Yuanyuan Kang and Bing Song

Biomedicines 2024, 12(3), 683; https://doi.org/10.3390/biomedicines12030683 - 19 Mar 2024

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Abstract

Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts a growing interest in stem cell therapy as a promising avenue for treatment. Dental-derived stem cells, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells [...] Read more.

Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts a growing interest in stem cell therapy as a promising avenue for treatment. Dental-derived stem cells, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells from the apical papilla (SCAP), dental follicle stem cells (DFSCs), are of interest due to their accessibility, minimally invasive extraction, and robust differentiating capabilities. Research indicates their potential to differentiate into neural cells and promote SCI repair in animal models at both tissue and functional levels. This review explores the potential applications of dental-derived stem cells in SCI neural repair, covering stem cell transplantation, conditioned culture medium injection, bioengineered delivery systems, exosomes, extracellular vesicle treatments, and combined therapies. Assessing the clinical effectiveness of dental-derived stem cells in the treatment of SCI, further research is necessary. This includes investigating potential biological mechanisms and conducting Large-animal studies and clinical trials. It is also important to undertake more comprehensive comparisons, optimize the selection of dental-derived stem cell types, and implement a functionalized delivery system. These efforts will enhance the therapeutic potential of dental-derived stem cells for repairing SCI. Full article

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

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22 pages, 2595 KiB

Open AccessReview

Rehabilitation Training after Spinal Cord Injury Affects Brain Structure and Function: From Mechanisms to Methods

by Le-Wei He, Xiao-Jun Guo, Can Zhao and Jia-Sheng Rao

Biomedicines 2024, 12(1), 41; https://doi.org/10.3390/biomedicines12010041 - 22 Dec 2023

Cited by 1 | Viewed by 1009

Abstract

Spinal cord injury (SCI) is a serious neurological insult that disrupts the ascending and descending neural pathways between the peripheral nerves and the brain, leading to not only functional deficits in the injured area and below the level of the lesion but also [...] Read more.

Spinal cord injury (SCI) is a serious neurological insult that disrupts the ascending and descending neural pathways between the peripheral nerves and the brain, leading to not only functional deficits in the injured area and below the level of the lesion but also morphological, structural, and functional reorganization of the brain. These changes introduce new challenges and uncertainties into the treatment of SCI. Rehabilitation training, a clinical intervention designed to promote functional recovery after spinal cord and brain injuries, has been reported to promote activation and functional reorganization of the cerebral cortex through multiple physiological mechanisms. In this review, we evaluate the potential mechanisms of exercise that affect the brain structure and function, as well as the rehabilitation training process for the brain after SCI. Additionally, we compare and discuss the principles, effects, and future directions of several rehabilitation training methods that facilitate cerebral cortex activation and recovery after SCI. Understanding the regulatory role of rehabilitation training at the supraspinal center is of great significance for clinicians to develop SCI treatment strategies and optimize rehabilitation plans. Full article

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

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20 pages, 2053 KiB

Open AccessReview

Differentiating Lumbar Spinal Etiology from Peripheral Plexopathies

by Marco Foreman, Krisna Maddy, Aashay Patel, Akshay Reddy, Meredith Costello and Brandon Lucke-Wold

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

Cited by 2 | Viewed by 5128

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 [...] Read more.

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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11 pages, 530 KiB

Open AccessReview

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

by 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

Cited by 1 | Viewed by 2803

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 [...] Read more.

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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16 pages, 742 KiB

Open AccessReview

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

by Ronak Reshamwala, Mariyam Murtaza, Mo Chen, Megha Shah, Jenny Ekberg, Dinesh Palipana, Marie-Laure Vial, Brent McMonagle and James St John

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

Cited by 1 | Viewed by 1635

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 [...] Read more.

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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