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

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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Faculty Opinions recommendation of Effect of vascular endothelial growth factor treatment in experimental traumatic spinal cord injury: in vivo longitudinal assessment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9908956.11172056 ◽

2011 ◽

Author(s):

Jose V Lafuente ◽

Enrike Argandoña

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vascular Endothelial Growth Factor ◽

Traumatic Spinal Cord Injury ◽

Vascular Endothelial ◽

Longitudinal Assessment ◽

Cord Injury ◽

Endothelial Growth Factor ◽

Growth Factor Treatment

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

Annals of Biomedical Engineering ◽

10.1007/s10439-015-1412-6 ◽

2015 ◽

Vol 44 (4) ◽

pp. 1285-1298 ◽

Cited By ~ 8

Author(s):

Tim Bhatnagar ◽

Jie Liu ◽

Andrew Yung ◽

Peter A. Cripton ◽

Piotr Kozlowski ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cervical Spinal Cord ◽

Rodent Model ◽

Traumatic Spinal Cord Injury ◽

In Vivo Measurement ◽

Cord Injury

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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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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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