In Vivo Measurement of Cervical Spinal Cord Deformation During Traumatic Spinal Cord Injury in a Rodent Model

Abstract Objectives Wallerian degeneration (WD) is a well-known process after nerve injury. In this study, occurrence of remote intramedullary signal changes, consistent with WD, and its correlation with clinical and neurophysiological impairment were assessed after traumatic spinal cord injury (tSCI). Methods In 35 patients with tSCI, WD was evaluated by two radiologists on T2-weighted images of serial routine MRI examinations of the cervical spine. Dorsal column (DC), lateral corticospinal tract (CS), and lateral spinothalamic tract (ST) were the analyzed anatomical regions. Impairment scoring according to the American Spinal Injury Association Impairment Scale (AIS, A–D) as well as a scoring system (0–4 points) for motor evoked potential (MEP) and sensory evoked potential (SEP) was included. Mann-Whitney U test was used to test for differences. Results WD in the DC occurred in 71.4% (n = 25), in the CS in 57.1% (n = 20), and in 37.1% (n = 13) in the ST. With WD present, AIS grades were worse for all tracts. DC: median AIS B vs D, p < 0.001; CS: B vs D, p = 0.016; and ST: B vs D, p = 0.015. More pathological MEP scores correlated with WD in the DC (median score 0 vs 3, p < 0.001) and in the CS (0 vs 2, p = 0.032). SEP scores were lower with WD in the DC only (1 vs 2, p = 0.031). Conclusions WD can be detected on T2-weighted scans in the majority of cervical spinal cord injury patients and should be considered as a direct effect of the trauma. When observed, it is associated with higher degree of impairment. Key Points • Wallerian degeneration is commonly seen in routine MRI after traumatic spinal cord injury. • Wallerian degeneration is visible in the anatomical regions of the dorsal column, the lateral corticospinal tract, and the lateral spinothalamic tract. • Presence of Wallerian degeneration is associated with higher degree of impairment.

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Harnessing the Secretome of Mesenchymal Stromal Cells for Traumatic Spinal Cord Injury: Multicell Comparison and Assessment of In Vivo Efficacy

Stem Cells and Development ◽

10.1089/scd.2020.0079 ◽

2020 ◽

Vol 29 (22) ◽

pp. 1429-1443

Author(s):

Reaz Vawda ◽

Anna Badner ◽

James Hong ◽

Mirriam Mikhail ◽

Rachel Dragas ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Traumatic Spinal Cord Injury ◽

In Vivo Efficacy ◽

Cord Injury

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Dual Differentiation-Exogenous Mesenchymal Stem Cell Therapy for Traumatic Spinal Cord Injury Repair in a Murine Hemisection Model

Stem Cells International ◽

10.1155/2013/928982 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Hai Liu ◽

Edward M. Schwarz ◽

Chao Xie

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Fracture Repair ◽

Critical Event ◽

In Vivo Model ◽

Traumatic Spinal Cord Injury ◽

Cord Injury

Mesenchymal stem cell (MSC) transplantation has shown tremendous promise as a therapy for repair of various tissues of the musculoskeletal, vascular, and central nervous systems. Based on this success, recent research in this field has focused on complex tissue damage, such as that which occurs from traumatic spinal cord injury (TSCI). As the critical event for successful exogenous, MSC therapy is their migration to the injury site, which allows for their anti-inflammatory and morphogenic effects on fracture healing, neuronal regeneration, and functional recover. Thus, there is a need for a cost-effective in vivo model that can faithfully recapitulate the salient features of the injury, therapy, and recovery. To address this, we review the recent advances in exogenous MSC therapy for TSCI and traumatic vertebral fracture repair and the existing challenges regarding their translational applications. We also describe a novel murine model designed to take advantage of multidisciplinary collaborations between musculoskeletal and neuroscience researchers, which is needed to establish an efficacious MSC therapy for TSCI.

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Evaluation of Traumatic Spinal Cord Injury in a Rat Model Using 99mTc-GA-5 as a Potential In Vivo Tracer

Molecules ◽

10.3390/molecules26237138 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7138

Author(s):

Vanessa Izquierdo-Sánchez ◽

Pablo C. Zambrano-Rodríguez ◽

Nadia Peña-Merino ◽

Sirio Bolaños-Puchet ◽

Horacio J. Reyes-Alva ◽

...

Keyword(s):

Spinal Cord ◽

Monoclonal Antibody ◽

Spinal Cord Injury ◽

Molecular Imaging ◽

In Vivo Imaging ◽

Practical Method ◽

Traumatic Spinal Cord Injury ◽

Recognition Specificity ◽

Cord Injury

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99mTc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5’s recognition/specificity ability were observed after the radiolabeling. The GA-5’s radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.

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The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms222312934 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12934

Author(s):

Mohammad-Masoud Zavvarian ◽

Cindy Zhou ◽

Sabah Kahnemuyipour ◽

James Hong ◽

Michael G. Fehlings

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Therapeutic Targets ◽

Mapk Signaling ◽

Transcriptional Analysis ◽

Traumatic Spinal Cord Injury ◽

Extracellular Matrix Components ◽

Cord Injury ◽

Species Specific

Despite the debilitating consequences following traumatic spinal cord injury (SCI), there is a lack of safe and effective therapeutics in the clinic. The species-specific responses to SCI present major challenges and opportunities for the clinical translation of biomolecular and pharmacological interventions. Recent transcriptional analyses in preclinical SCI studies have provided a snapshot of the local SCI-induced molecular responses in different animal models. However, the variation in the pathogenesis of traumatic SCI across species is yet to be explored. This study aims to identify and characterize the common and inconsistent SCI-induced differentially expressed genes across species to identify potential therapeutic targets of translational relevance. A comprehensive search of open-source transcriptome datasets identified four cross-compatible microarray experiments in rats, mice, and salamanders. We observed consistent expressional changes in extracellular matrix components across the species. Conversely, salamanders showed downregulation of intracellular MAPK signaling compared to rodents. Additionally, sequence conservation and interactome analyses highlighted the well-preserved sequences of Fn1 and Jun with extensive protein-protein interaction networks. Lastly, in vivo immunohistochemical staining for fibronectin was used to validate the observed expressional pattern. These transcriptional changes in extracellular and MAPK pathways present potential therapeutic targets for traumatic SCI with promising translational relevance.

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Clinical Characteristics and Challenges of Management of Traumatic Spinal Cord Injury in a Trauma Center of a Developing Country

Journal of Neurosciences in Rural Practice ◽

10.1055/s-0039-1695696 ◽

2019 ◽

Vol 10 (03) ◽

pp. 393-399

Author(s):

Ayodeji Salman Yusuf ◽

Muhammad Raji Mahmud ◽

Dumura Jeneral Alfin ◽

Samue Isa Gana ◽

Samaila Timothy ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Trauma Center ◽

Spinal Injury ◽

Cervical Spinal Cord ◽

Prehospital Care ◽

Insurance Coverage ◽

Traumatic Spinal Cord Injury ◽

Optimal Care ◽

Cord Injury

Abstract Background Traumatic spinal cord injury (TSCI) is a major burden in trauma care worldwide. Most victims are young, and the injury results in economic loss and psychological and social burden on the individual and the society. The outcome depends on the severity of primary spinal cord injury, interventions to prevent secondary insults to the damaged cord, and access to a specialized care. The lack of standard prehospital care and dedicated facilities for spine care coupled with challenges of inadequate health insurance coverage impact negatively on the outcome of care in patients with spinal cord injury in our practice. Objectives This study was performed to determine the clinical profile of patients with TSCI and to highlight the factors that determine the early outcome in a resource-constrained trauma center. Materials and Methods This study was a retrospective review of trauma registry and medical records of all the patients with acute TSCI at the National Trauma Center Abuja from September 2014 to December 2016. Results A total of 133 patients with TSCI were studied. Most of these patients were young men with a mean age of 36 years. Most injury (72.2%) occurred following motor vehicular crash affecting mainly the cervical spinal cord (62.0%). None of the patients received standard prehospital care. Only 41.4% of the patients were transported to the hospital in an ambulance. About half (52.6%) of the patients suffered complete spinal cord injury (the American Spinal Injury Association [ASIA] A), and pressure ulcer was the most common complication (23.3%). Only 42% of the patients that needed surgical intervention were operated, mainly due to the inability to pay for the service. The ASIA grade on admission was the most significant determinant factor of morbidity and mortality. Conclusion Optimal care of patients with TSCI was hindered by inadequate facilities and economic constraints.

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Characterization of a Novel, Magnetic Resonance Imaging-Compatible Rodent Model Spinal Cord Injury Device

Journal of Biomechanical Engineering ◽

10.1115/1.4027670 ◽

2014 ◽

Vol 136 (9) ◽

Cited By ~ 7

Author(s):

Tim Bhatnagar ◽

Jie Liu ◽

Thomas Oxland

Keyword(s):

Magnetic Resonance Imaging ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Magnetic Resonance ◽

High Speed ◽

Cervical Spinal Cord ◽

Rodent Model ◽

Resonance Imaging ◽

Biological Damage ◽

Cord Injury

Rodent models of acute spinal cord injury (SCI) are often used to investigate the effects of injury mechanism, injury speed, and cord displacement magnitude, on the ensuing cascade of biological damage in the cord. However, due to its small size, experimental observations have largely been limited to the gross response of the cord. To properly understand the relationship between mechanical stimulus and biological damage, more information is needed about how the constituent tissues of the cord (i.e., gray and white matter) respond to injurious stimuli. To address this limitation, we developed a novel magnetic resonance imaging (MRI)-compatible test apparatus that can impose either a contusion-type or dislocation-type acute cervical SCI in a rodent model and facilitate MR-imaging of the cervical spinal cord in a 7 T MR scanner. In this study, we present the experimental performance parameters of the MR rig. Utilizing cadaveric specimens and static radiographs, we report contusion magnitude accuracy that for a desired 1.8 mm injury, a nominal 1.78 mm injury (SD = 0.12 mm) was achieved. High-speed video analysis was employed to determine the injury speeds for both mechanisms and were found to be 1147 mm/s (SD = 240 mm/s) and 184 mm/s (SD = 101 mm/s) for contusion and dislocation injuries, respectively. Furthermore, we present qualitative pilot data from a cadaveric trial, employing the MR rig, to show the expected results from future studies.

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