Biomedicines

Research

19 pages, 4576 KiB

Open AccessArticle

Functional State of the Motor Centers of the Lumbar Spine after Contusion (Th8-Th9) with Application of Methylprednisolone-Copolymer at the Site of Injury

by Maxim Baltin, Victoriya Smirnova, Regina Khamatnurova, Diana Sabirova, Bulat Samigullin, Oskar Sachenkov and Tatyana Baltina

Biomedicines 2023, 11(7), 2026; https://doi.org/10.3390/biomedicines11072026 - 18 Jul 2023

Viewed by 1459

Abstract

Spinal cord injuries must be treated as soon as possible. Studies of NASCIS protocols have questioned the use of methylprednisolone therapy. This study aimed to evaluate the effect of local delivery of methylprednisolone succinate in combination with a tri-block copolymer in rats with [...] Read more.

Spinal cord injuries must be treated as soon as possible. Studies of NASCIS protocols have questioned the use of methylprednisolone therapy. This study aimed to evaluate the effect of local delivery of methylprednisolone succinate in combination with a tri-block copolymer in rats with spinal cord injury. The experiments were conducted in accordance with the bioethical guidelines. We evaluated the state of the motor centers below the level of injury by assessing the amplitude of evoked motor responses in the hind limb muscles of rats during epidural stimulation. Kinematic analysis was performed to examine the stepping cycle in each rat. Trajectories of foot movements were plotted to determine the range of limb motion, maximum foot lift height, and lateral deviation of the foot in rats on the 21st day after spinal cord injury. We have shown that the local application of methylprednisolone succinate in combination with block copolymer leads to recovery of center excitability by 21 days after injury. In rats, they recovered weight-supported locomotion, directional control of walking, and balance. The proposed assessment method provides valuable information on gait disturbances following injury and can be utilized to evaluate the quality of therapeutic interventions. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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27 pages, 3985 KiB

Open AccessArticle

MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord

by Rodrigo M. Maza, María Asunción Barreda-Manso, David Reigada, Ágata Silván, Teresa Muñoz-Galdeano, Altea Soto, Ángela del Águila and Manuel Nieto-Díaz

Biomedicines 2022, 10(7), 1559; https://doi.org/10.3390/biomedicines10071559 - 30 Jun 2022

Cited by 5 | Viewed by 2535

Abstract

The central nervous system microRNA miR-138-5p has attracted much attention in cancer research because it inhibits pro-apoptotic genes including CASP3. We hypothesize that miR-138-5p downregulation after SCI leads to overexpression of pro-apoptotic genes, sensitizing neural cells to noxious stimuli. This study aimed to [...] Read more.

The central nervous system microRNA miR-138-5p has attracted much attention in cancer research because it inhibits pro-apoptotic genes including CASP3. We hypothesize that miR-138-5p downregulation after SCI leads to overexpression of pro-apoptotic genes, sensitizing neural cells to noxious stimuli. This study aimed to identify miR-138-5p targets among pro-apoptotic genes overexpressed following SCI and to confirm that miR-138-5p modulates cell death in neural cells. Gene expression and histological analyses revealed that the drop in miR-138-5p expression after SCI is due to the massive loss of neurons and oligodendrocytes and its downregulation in neurons. Computational analyses identified 176 potential targets of miR-138-5p becoming dysregulated after SCI, including apoptotic proteins CASP-3 and CASP-7, and BAK. Reporter, RT-qPCR, and immunoblot assays in neural cell cultures confirmed that miR-138-5p targets their 3′UTRs, reduces their expression and the enzymatic activity of CASP-3 and CASP-7, and protects cells from apoptotic stimuli. Subsequent RT-qPCR and histological analyses in a rat model of SCI revealed that miR-138-5p downregulation correlates with the overexpression of its pro-apoptotic targets. Our results suggest that the downregulation of miR-138-5p after SCI may have deleterious effects on neural cells, particularly on spinal neurons. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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16 pages, 3162 KiB

Open AccessArticle

Human Epidural AD–MSC Exosomes Improve Function Recovery after Spinal Cord Injury in Rats

by Soo-Eun Sung, Min-Soo Seo, Young-In Kim, Kyung-Ku Kang, Joo-Hee Choi, Sijoon Lee, Minkyoung Sung, Sang-Gu Yim, Ju-Hyeon Lim, Hyun-Gyu Seok, Seung-Yun Yang and Gun-Woo Lee

Biomedicines 2022, 10(3), 678; https://doi.org/10.3390/biomedicines10030678 - 15 Mar 2022

Cited by 26 | Viewed by 3468

Abstract

Spinal cord injury (SCI) interferes with the normal function of the autonomic nervous system by blocking circuits between the sensory and motor nerves. Although many studies focus on functional recovery after neurological injury, effective neuroregeneration is still being explored. Recently, extracellular vesicles such [...] Read more.

Spinal cord injury (SCI) interferes with the normal function of the autonomic nervous system by blocking circuits between the sensory and motor nerves. Although many studies focus on functional recovery after neurological injury, effective neuroregeneration is still being explored. Recently, extracellular vesicles such as exosomes have emerged as cell-free therapeutic agents owing to their ability of cell-to-cell communication. In particular, exosomes released from mesenchymal stem cells (MSCs) have the potential for tissue regeneration and exhibit therapeutic effectiveness in neurological disorders. In this study, we isolated exosomes from human epidural adipose tissue-derived MSCs (hEpi AD–MSCs) using the tangential flow filtration method. The isolated exosomes were analyzed for size, concentration, shape, and major surface markers using nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry. To evaluate their effect on SCI recovery, hEpi AD–MSC exosomes were injected intravenously in SCI-induced rats. hEpi AD–MSC exosomes improved the locomotor function of SCI-induced rats. The results of histopathological and cytokine assays showed that hEpi AD–MSC exosomes regulated inflammatory response. Genetic profiling of the rat spinal cord tissues revealed changes in the expression of inflammation-related genes after exosome administration. Collectively, hEpi AD–MSC exosomes are effective in restoring spinal functions by reducing the inflammatory response. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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18 pages, 2834 KiB

Open AccessArticle

Transplanting Neural Progenitor Cells into a Chronic Dorsal Column Lesion Model

by Kazuo Hayakawa, Ying Jin, Julien Bouyer, Theresa M. Connors, Takanobu Otsuka and Itzhak Fischer

Biomedicines 2022, 10(2), 350; https://doi.org/10.3390/biomedicines10020350 - 1 Feb 2022

Cited by 4 | Viewed by 1985

Abstract

Cell transplantation therapy is a promising strategy for spinal cord injury (SCI) repair. Despite advancements in the development of therapeutic strategies in acute and subacute SCI, much less is known about effective strategies for chronic SCI. In previous studies we demonstrated that transplants [...] Read more.

Cell transplantation therapy is a promising strategy for spinal cord injury (SCI) repair. Despite advancements in the development of therapeutic strategies in acute and subacute SCI, much less is known about effective strategies for chronic SCI. In previous studies we demonstrated that transplants of neural progenitor cells (NPC) created a permissive environment for axon regeneration and formed a neuronal relay across the injury following an acute dorsal column injury. Here we explored the efficacy of such a strategy in a chronic injury. We tested two preparations of NPCs derived from rat spinal cord at embryonic day 13.5: one prepared using stocks of cultured cells and the other of dissociated cells transplanted without culturing. Transplantation was delayed for 4-, 6- and 12-weeks post injury for a chronic injury model. We found that the dissociated NPC transplants survived and proliferated for at least 5 weeks post transplantation, in contrast to the poor survival of transplants prepared from cultured NPC stocks. The dissociated NPC transplants differentiated into neurons expressing excitatory markers, promoted axon regeneration into the injury/transplant site and extended axons from graft-derived neurons into the host. These results support the potential of NPC transplants to form neuronal relays across a chronic SCI, but they also underscore the challenges of achieving efficient cell survival in the environment of a chronic injury. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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13 pages, 3887 KiB

Open AccessArticle

Treatment with Pulsed Extremely Low Frequency Electromagnetic Field (PELF-EMF) Exhibit Anti-Inflammatory and Neuroprotective Effect in Compression Spinal Cord Injury Model

by Yona Goldshmit, Moshe Shalom and Angela Ruban

Biomedicines 2022, 10(2), 325; https://doi.org/10.3390/biomedicines10020325 - 29 Jan 2022

Cited by 5 | Viewed by 4147

Abstract

Background: Spinal cord injury (SCI) pathology includes both primary and secondary events. The primary injury includes the original traumatic event, and the secondary injury, beginning immediately after the initial injury, involves progressive neuroinflammation, neuronal excitotoxicity, gliosis, and degeneration. Currently, there is no effective [...] Read more.

Background: Spinal cord injury (SCI) pathology includes both primary and secondary events. The primary injury includes the original traumatic event, and the secondary injury, beginning immediately after the initial injury, involves progressive neuroinflammation, neuronal excitotoxicity, gliosis, and degeneration. Currently, there is no effective neuroprotective treatment for SCI. However, an accumulating body of data suggests that PELF-EMF has beneficial therapeutic effects on neurotrauma. The purpose of this study was to test the efficacy of the PELF-EMF SEQEX device using a compression SCI mouse model. Methods: C57BL/6 mice were exposed to PELF-EMF for 4 h on a daily basis for two months, beginning 2 h after a mild-moderate compression SCI. Results: The PELF-EMF treatment significantly diminished inflammatory cell infiltration and astrocyte activation by reducing Iba1, F4/80, CD68+ cells, and GAFP at the lesion borders, and increased pro-survival signaling, such as BDNF, on the neuronal cells. Moreover, the treatment exhibited a neuroprotective effect by reducing the demyelination of the axons of the white matter at the lesion’s center. Conclusions: Treatment with SEQEX demonstrated significant anti-inflammatory and neuroprotective effects. Considering our results, this safe and effective rehabilitative device, already available on the market, may provide a major therapeutic asset in the treatment of SCI. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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Review

Jump to: Research, Other

21 pages, 2749 KiB

Open AccessReview

Biomaterial-Mediated Factor Delivery for Spinal Cord Injury Treatment

by Filippo Pinelli, Fabio Pizzetti, Valeria Veneruso, Emilia Petillo, Michael Raghunath, Giuseppe Perale, Pietro Veglianese and Filippo Rossi

Biomedicines 2022, 10(7), 1673; https://doi.org/10.3390/biomedicines10071673 - 12 Jul 2022

Cited by 11 | Viewed by 3745

Abstract

Spinal cord injury (SCI) is an injurious process that begins with immediate physical damage to the spinal cord and associated tissues during an acute traumatic event. However, the tissue damage expands in both intensity and volume in the subsequent subacute phase. At this [...] Read more.

Spinal cord injury (SCI) is an injurious process that begins with immediate physical damage to the spinal cord and associated tissues during an acute traumatic event. However, the tissue damage expands in both intensity and volume in the subsequent subacute phase. At this stage, numerous events exacerbate the pathological condition, and therein lies the main cause of post-traumatic neural degeneration, which then ends with the chronic phase. In recent years, therapeutic interventions addressing different neurodegenerative mechanisms have been proposed, but have met with limited success when translated into clinical settings. The underlying reasons for this are that the pathogenesis of SCI is a continued multifactorial disease, and the treatment of only one factor is not sufficient to curb neural degeneration and resulting paralysis. Recent advances have led to the development of biomaterials aiming to promote in situ combinatorial strategies using drugs/biomolecules to achieve a maximized multitarget approach. This review provides an overview of single and combinatorial regenerative-factor-based treatments as well as potential delivery options to treat SCIs. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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13 pages, 1078 KiB

Open AccessReview

Neuroprotective Role of Hypothermia in Acute Spinal Cord Injury

by Hasan Al-Nashash and Angelo H. ALL

Biomedicines 2022, 10(1), 104; https://doi.org/10.3390/biomedicines10010104 - 4 Jan 2022

Cited by 4 | Viewed by 2196

Abstract

Even nowadays, the question of whether hypothermia can genuinely be considered therapeutic care for patients with traumatic spinal cord injury (SCI) remains unanswered. Although the mechanisms of hypothermia action are yet to be fully explored, early hypothermia for patients suffering from acute SCI [...] Read more.

Even nowadays, the question of whether hypothermia can genuinely be considered therapeutic care for patients with traumatic spinal cord injury (SCI) remains unanswered. Although the mechanisms of hypothermia action are yet to be fully explored, early hypothermia for patients suffering from acute SCI has already been implemented in clinical settings. This article discusses measures for inducing various forms of hypothermia and summarizes several hypotheses describing the likelihood of hypothermia mechanisms of action. We present our objective neuro-electrophysiological results and demonstrate that early hypothermia manifests neuroprotective effects mainly during the first- and second-month post-SCI, depending on the severity of the injury, time of intervening, duration, degree, and modality of inducing hypothermia. Nevertheless, eventually, its beneficial effects gradually but consistently diminish. In addition, we report potential complications and side effects for the administration of general hypothermia with a unique referment to the local hypothermia. We also provide evidence that instead of considering early hypothermia post-SCI a therapeutic approach, it is more a neuroprotective strategy in acute and sub-acute phases of SCI that mostly delay, but not entirely avoid, the natural history of the pathophysiological events. Indeed, the most crucial rationale for inducing early hypothermia is to halt these devastating inflammatory and apoptotic events as early and as much as possible. This, in turn, creates a larger time-window of opportunity for physicians to formulate and administer a well-designed personalized treatment for patients suffering from acute traumatic SCI. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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Other

Jump to: Research, Review

14 pages, 927 KiB

Open AccessPerspective

Future Treatment of Neuropathic Pain in Spinal Cord Injury: The Challenges of Nanomedicine, Supplements or Opportunities?

by Giuseppe Forte, Valentina Giuffrida, Angelica Scuderi and Mariella Pazzaglia

Biomedicines 2022, 10(6), 1373; https://doi.org/10.3390/biomedicines10061373 - 10 Jun 2022

Cited by 10 | Viewed by 5246

Abstract

Neuropathic pain (NP) is a common chronic condition that severely affects patients with spinal cord injuries (SCI). It impairs the overall quality of life and is considered difficult to treat. Currently, clinical management of NP is often limited to drug therapy, primarily with [...] Read more.

Neuropathic pain (NP) is a common chronic condition that severely affects patients with spinal cord injuries (SCI). It impairs the overall quality of life and is considered difficult to treat. Currently, clinical management of NP is often limited to drug therapy, primarily with opioid analgesics that have limited therapeutic efficacy. The persistence and intractability of NP following SCI and the potential health risks associated with opioids necessitate improved treatment approaches. Nanomedicine has gained increasing attention in recent years for its potential to improve therapeutic efficacy while minimizing toxicity by providing sensitive and targeted treatments that overcome the limitations of conventional pain medications. The current perspective begins with a brief discussion of the pathophysiological mechanisms underlying NP and the current pain treatment for SCI. We discuss the most frequently used nanomaterials in pain diagnosis and treatment as well as recent and ongoing efforts to effectively treat pain by proactively mediating pain signals following SCI. Although nanomedicine is a rapidly growing field, its application to NP in SCI is still limited. Therefore, additional work is required to improve the current treatment of NP following SCI. Full article

(This article belongs to the Special Issue Spinal Cord Injury: From Mechanisms to Nanotherapeutic Approaches)

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