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Cellular and Molecular Biology of Spinal Cord Injury

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 9648

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Special Issue Editor

Dr. Tae Sik Goh

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Guest Editor

College of Medicine, Pusan National University, Busan, Korea
Interests: spine; scoliosis; spinal biomechanics; cytokine receptors; osteoimmunology; applied artificial intelligence

Special Issue Information

Dear Colleagues,

Spinal cord injury (SCI), for which there currently is no cure, is a heavy burden on patient physiology and psychology. SCIs is known to produce a myriad of effects over the acute, sub-acute, and chronic period following an injury, including paralysis, altered sensation below the level of the injury, as well as aberrant autonomic responses. This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration. Over the subsequent hours, release of proinflammatory cytokines and cytotoxic debris (DNA, ATP, reactive oxygen species) cyclically adds to the harsh postinjury microenvironment. As the lesions mature into the chronic phase, regeneration is severely impeded by the development of an astroglial-fibrous scar surrounding coalesced cystic cavities. Addressing these challenges forms the basis of current and upcoming treatments for SCI.

As such, a Special Issue dedicated to the current understanding of cellular and molecular biology after spinal cord injury is warranted. Original research articles or reviews on SCI related to the molecular and cellular mechanisms through which Spinal cord injury can be treated are welcome. Articles with insights on biological and therapeutic perspectives are especially welcome.

Dr. Tae Sik Goh
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

spine
spinal cord injury
neuroprotection
extracellular vesicles
cytokine receptors
stem cells

Published Papers (5 papers)

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Research

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19 pages, 60572 KiB

Open AccessArticle

Tibolone Improves Locomotor Function in a Rat Model of Spinal Cord Injury by Modulating Apoptosis and Autophagy

by Stephanie Sánchez-Torres, Carlos Orozco-Barrios, Hermelinda Salgado-Ceballos, Julia J. Segura-Uribe, Christian Guerra-Araiza, Ángel León-Cholula, Julio Morán and Angélica Coyoy-Salgado

Int. J. Mol. Sci. 2023, 24(20), 15285; https://doi.org/10.3390/ijms242015285 - 18 Oct 2023

Cited by 1 | Viewed by 987

Abstract

Spinal cord injury (SCI) harms patients’ health and social and economic well-being. Unfortunately, fully effective therapeutic strategies have yet to be developed to treat this disease, affecting millions worldwide. Apoptosis and autophagy are critical cell death signaling pathways after SCI that should be targeted for early therapeutic interventions to mitigate their adverse effects and promote functional recovery. Tibolone (TIB) is a selective tissue estrogen activity regulator (STEAR) with neuroprotective properties demonstrated in some experimental models. This study aimed to investigate the effect of TIB on apoptotic cell death and autophagy after SCI and verify whether TIB promotes motor function recovery. A moderate contusion SCI was produced at thoracic level 9 (T9) in male Sprague Dawley rats. Subsequently, animals received a daily dose of TIB orally and were sacrificed at 1, 3, 14 or 30 days post-injury. Tissue samples were collected for morphometric and immunofluorescence analysis to identify tissue damage and the percentage of neurons at the injury site. Autophagic (Beclin-1, LC3-I/LC3-II, p62) and apoptotic (Caspase 3) markers were also analyzed via Western blot. Finally, motor function was assessed using the BBB scale. TIB administration significantly increased the amount of preserved tissue (p < 0.05), improved the recovery of motor function (p < 0.001) and modulated the expression of autophagy markers in a time-dependent manner while consistently inhibiting apoptosis (p < 0.05). Therefore, TIB could be a therapeutic alternative for the recovery of motor function after SCI. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Spinal Cord Injury)

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20 pages, 2898 KiB

Open AccessArticle

Rosuvastatin Synergistically Enhances the Antinociceptive Efficacy of Duloxetine in Paclitaxel-Induced Neuropathic Pain in Mice

by Nicolás Lobos, Sebastián Lux, Ramiro Javier Zepeda, Teresa Pelissier, José Luis Marcos, Gonzalo Bustos-Quevedo, Alejandro Hernández and Luis Constandil

Int. J. Mol. Sci. 2023, 24(9), 8359; https://doi.org/10.3390/ijms24098359 - 6 May 2023

Viewed by 1838

Abstract

Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED₃₀, von Frey testing) and thermal hyperalgesia (ED₅₀, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED₃₀ and ED₅₀ for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Spinal Cord Injury)

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34 pages, 10606 KiB

Open AccessArticle

Patients with Chronic Spinal Cord Injury and a Long Period of Evolution Exhibit an Altered Cytokine Production by CD4 and CD8 T Cell Populations

by Sergio Haro Girón, Ana M. Gómez-Lahoz, Jorge Monserrat Sanz, Oscar Fraile-Martínez, Diego J. Jiménez, Cielo Garcia-Montero, Diego de Leon-Oliva, Miguel A. Ortega, Mar Atienza-Perez, David Diaz, Elisa Lopez-Dolado and Melchor Álvarez-Mon

Int. J. Mol. Sci. 2023, 24(8), 7048; https://doi.org/10.3390/ijms24087048 - 11 Apr 2023

Cited by 6 | Viewed by 1550

Abstract

Spinal cord injury (SCI) is a disabling neurological condition coursing with serious multisystem affections and morbidities. Changes in immune cell compartments have been consistently reported in previous works, representing a critical point of study for understanding the pathophysiology and progression of SCI from acute to chronic stages. Some relevant variations in circulating T cells have been noticed in patients with chronic SCI, although the number, distribution, and function of these populations remain to be fully elucidated. Likewise, the characterization of specific T cell subpopulations and their related cytokine production can aid in understanding the immunopathological role of T cells in SCI progression. In this sense, the objective of the present study was to analyze and quantify the total number of different cytokine-producers T cells in the serum of patients with chronic SCI (n = 105) in comparison to healthy controls (n = 38) by polychromatic flow cytometry. Having this goal, we studied CD4 and CD8 lymphocytes as well as naïve, effector, and effector/central memory subpopulations. SCI patients were classified according to the duration of the lesion in chronic SCI with a short period of evolution (SCI-SP) (comprised between 1 and 5 years since initial injury), early chronic phase (SCI-ECP) (between 5 and 15 years since initial injury) and late-chronic phase (SCI-LCP) (>15 years since initial injury). Our results show that patients with chronic SCI exhibited an altered immune profile of cytokine-producer T cells, including CD4/CD8 naïve, effector, and memory subpopulations in comparison to HC. In particular, IL-10 and IL-9 production seems to be importantly altered, especially in patients with SCI-LCP, whereas changes in IL-17, TNF-α, and IFN-γ T cell populations have also been reported in this and other chronic SCI groups. In conclusion, our study demonstrates an altered profile of cytokine-producer T cells in patients with chronic SCI, with marked changes throughout the course of the disease. In more detail, we have observed significant variations in cytokine production by circulating naive, effector, and effector/central memory CD4 and CD8 T cells. Future studies should be directed to explore the possible clinical consequences of these changes or develop additional translational approaches in these groups of patients. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Spinal Cord Injury)

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23 pages, 4154 KiB

Open AccessArticle

Transient Reflexive Pain Responses and Chronic Affective Nonreflexive Pain Responses Associated with Neuroinflammation Processes in Both Spinal and Supraspinal Structures in Spinal Cord-Injured Female Mice

by Sílvia Castany, Anna Bagó-Mas, José Miguel Vela, Enrique Verdú, Karolina Bretová, Viktorie Svobodová, Petr Dubový and Pere Boadas-Vaello

Int. J. Mol. Sci. 2023, 24(2), 1761; https://doi.org/10.3390/ijms24021761 - 16 Jan 2023

Viewed by 2256

Abstract

Central neuropathic pain is not only characterized by reflexive pain responses, but also emotional or affective nonreflexive pain responses, especially in women. Some pieces of evidence suggest that the activation of the neuroimmune system may be contributing to the manifestation of mood disorders in patients with chronic pain conditions, but the mechanisms that contribute to the development and chronicity of CNP and its associated disorders remain poorly understood. This study aimed to determine whether neuroinflammatory factor over-expression in the spinal cord and supraspinal structures may be associated with reflexive and nonreflexive pain response development from acute SCI phase to 12 weeks post-injury in female mice. The results show that transient reflexive responses were observed during the SCI acute phase associated with transient cytokine overexpression in the spinal cord. In contrast, increased nonreflexive pain responses were observed in the chronic phase associated with cytokine overexpression in supraspinal structures, especially in mPFC. In addition, results revealed that besides cytokines, the mPFC showed an increased glial activation as well as CX3CL1/CX3CR1 upregulation in the neurons, suggesting the contribution of neuron-glia crosstalk in the development of nonreflexive pain responses in the chronic spinal cord injury phase. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Spinal Cord Injury)

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Review

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20 pages, 1473 KiB

Open AccessReview

Stem Cell Strategies in Promoting Neuronal Regeneration after Spinal Cord Injury: A Systematic Review

by Lapo Bonosi, Manikon Poullay Silven, Antonio Alessandro Biancardino, Andrea Sciortino, Giuseppe Roberto Giammalva, Alba Scerrati, Carmelo Lucio Sturiale, Alessio Albanese, Silvana Tumbiolo, Massimiliano Visocchi, Domenico Gerardo Iacopino and Rosario Maugeri

Int. J. Mol. Sci. 2022, 23(21), 12996; https://doi.org/10.3390/ijms232112996 - 27 Oct 2022

Cited by 3 | Viewed by 2407

Abstract

Spinal cord injury (SCI) is a devastating condition with a significant medical and socioeconomic impact. To date, no effective treatment is available that can enable neuronal regeneration and recovery of function at the damaged level. This is thought to be due to scar formation, axonal degeneration and a strong inflammatory response inducing a loss of neurons followed by a cascade of events that leads to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their ability to differentiate into neuronal cells and release neurotrophic factors. Therefore, it appears to be a valid strategy to use in the field of regenerative medicine. This review aims to provide an up-to-date summary of the current research status, challenges, and future directions for stem cell therapy in SCI models, providing an overview of this constantly evolving and promising field. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Spinal Cord Injury)

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