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Updated: Jun 28, 2026
Calibrated Forceps Model of Spinal Cord Compression Injury
Published on: April 24, 2015
Comparative analysis of the time-dependent functional and molecular changes in spinal cord degeneration induced by
Andrea Malaspina1, Natasa Jokic, Wenlong L Huang
1Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, Whitechapel, London E1 2AT, UK. a.malaspina@qmul.ac.uk
Background:
Mutations of the superoxide dismutase 1 (SOD1) gene are linked to amyotrophic lateral sclerosis (ALS), an invariably fatal neurological condition involving cortico-spinal degeneration. Mechanical injury can also determine spinal cord degeneration and act as a risk factor for the development of ALS.
Results:
We have performed a comparative ontological analysis of the gene expression profiles of thoracic cord samples from rats carrying the G93A SOD1 gene mutation and from wild-type littermates subjected to mechanical compression of the spinal cord. Common molecular responses and gene expression changes unique to each experimental paradigm were evaluated against the functional development of each animal model. Gene Ontology categories crucial to protein folding, extracellular matrix and axonal formation underwent early activation in both experimental paradigms, but decreased significantly in the spinal cord from animals recovering from injury after 7 days and from the G93A SOD1 mutant rats at end-stage disease. Functional improvement after compression coincided with a massive up-regulation of growth-promoting gene categories including factors involved in angiogenesis and transcription, overcoming the more transitory surge of pro-apoptotic components and cell-cycle genes. The cord from G93A SOD1 mutants showed persistent over-expression of apoptotic and stress molecules with fewer neurorestorative signals, while functional deterioration was ongoing.
Conclusion:
this study illustrates how cytoskeletal protein metabolism is central to trauma and genetically-induced spinal cord degeneration and elucidates the main molecular events accompanying functional recovery or decline in two different animal models of spinal cord degeneration.
Insights
Spinal cord degeneration, whether from genetic mutations or injury, involves cytoskeletal protein changes. Recovery is linked to growth factors, while disease progression shows persistent stress signals.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Mutations in the superoxide dismutase 1 (SOD1) gene are associated with amyotrophic lateral sclerosis (ALS).
- Mechanical spinal cord injury is a risk factor for ALS development.
- Both SOD1 mutations and mechanical injury cause spinal cord degeneration.
Purpose of the Study:
- To comparatively analyze gene expression profiles in rat models of genetic and traumatic spinal cord degeneration.
- To identify common and unique molecular responses to SOD1 mutations and mechanical injury.
- To correlate molecular events with functional recovery and decline in these models.
Main Methods:
- Comparative ontological analysis of thoracic cord gene expression profiles.
- Utilized G93A SOD1 mutant rats and wild-type rats subjected to mechanical spinal cord compression.
- Evaluated gene expression changes against functional outcomes in both experimental paradigms.
Main Results:
- Early activation of protein folding, extracellular matrix, and axonal formation genes in both models.
- Decreased activation of these categories during recovery from injury and in end-stage SOD1 mutants.
- Functional recovery after compression correlated with up-regulation of growth-promoting genes (angiogenesis, transcription).
- G93A SOD1 mutants showed persistent overexpression of apoptotic/stress molecules and fewer neurorestorative signals.
Conclusions:
- Cytoskeletal protein metabolism is central to both trauma- and genetically-induced spinal cord degeneration.
- Distinct molecular events accompany functional recovery (growth factors) versus decline (stress molecules).
- This study elucidates key molecular pathways in spinal cord degeneration and recovery.
