A novel experimental model of cervical spondylotic myelopathy (CSM) to facilitate translational research

Karadimas, Spyridon K.; Moon, Eun Su; Yu, Wen-Ru; Satkunendrarajah, Kajana; Kallitsis, Joannis K.; Gatzounis, George; Fehlings, Michael G.

doi:10.1016/j.nbd.2013.02.013

Cited by 113 publications

(129 citation statements)

References 41 publications

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“…6,33 In this study, we show extensive neurodegeneration several segments above the level of compression in the spinal ventral and dorsal horns in-vivo. Interestingly, the ventral horns showed diffusivity changes (i.e.…”

Section: Insights Into Spinal Cord Grey Matter Pathologysupporting

confidence: 52%

Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Grabher

Mohammadi

Dávid

et al. 2017

Journal of Neurotrauma

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Remote grey matter pathology has been suggested rostral to the compression site in cervical spondylotic myelopathy (CSM). We used computational neuroimaging to assess in-vivo the extent and functional relevance of neurodegeneration in ventral and dorsal horns above the site of compression in the cervical cord of CSM patients. Twenty patients with CSM and eighteen healthy subjects underwent a high-resolution structural and diffusion MRI protocol at vertebra C2/C3. Patients received comprehensive clinical assessments. T2*-weighted data were used to segment the cross-sectional area of the grey matter into the ventral and dorsal horns. Within the ventral and dorsal horns mean diffusivity (MD) and fractional anisotropy (FA) derived from diffusion tensor imaging data determined the underlying microstructural integrity. Finally, the relationships between neurodegeneration occurring in the grey and white matter and clinical impairment were investigated. Patients suffered from mild to moderate CSM with mainly sensory impairment. The cross-sectional area of the ventral horns was not reduced (p=0.863) when compared to controls, but MD was increased (p=0.045). Greater increases in MD within the ventral horn were associated with white matter diffusivity changes (increased MD: p=0.013; decreased FA: p=0.028) within the lateral corticospinal tract. In contrast, dorsal horn cross-sectional area was reduced by 16.0% (p<0.001) without alterations in diffusivity indices when compared to controls. No associations between neurodegeneration and clinical impairment were evident. Grey matter atrophy and microstructural changes are evident remote to the compression site in CSM patients. Prior to marked motor impairment, pathophysiological changes in the ventral horns (e.g. motoneurons) related to white matter changes within the corticospinal tract. Thus, neuroimaging biomarkers of cord grey matter integrity reveal focal neurodegeneration prior to marked clinical impairment and thus could serve as predictors of ensuing impairment in CSM patients. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. AbstractRemote grey matter pathology has been suggested rostral to the compression site in cervical spondylotic myelopathy (CSM). We therefore assessed neurodegeneration in the grey matter ventral and dorsal horns.Twenty patients with CSM and eighteen healthy subjects underwent a high-...

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Section: Insights Into Spinal Cord Grey Matter Pathologysupporting

confidence: 52%

Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Grabher

Mohammadi

Dávid

et al. 2017

Journal of Neurotrauma

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“…Moreover, many of these models entail compression not in the cervical spinal cord, but in the thoracic area. These limitations leave a gap necessitating the study of the spinal cord blood flow in experimental models which are characterized by slow progressive compression at the C5-C6 level [27,28].…”

Section: Ischemiamentioning

confidence: 99%

Pathobiology of cervical spondylotic myelopathy

2014

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In this narrative review, we aim to outline what is currently known about the pathophysiology of cervical spondylotic myelopathy (CSM), the most common cause of spinal cord dysfunction. In particular, we note the unique factors that distinguish it from acute spinal cord injury. Despite its common occurrence, the reasons why some patients develop severe symptomatology while others have few or no symptoms despite radiographic evidence confirming similar degrees of compression is poorly understood. Neither is there a clear understanding of why certain patients have a stable clinical myelopathy and others present with only mild myelopathy. Moreover, the precise molecular mechanisms which contribute to the pathogenesis of the disease are incompletely understood. The current treatment method is decompression of the spinal cord but a lack of clinically relevant models of CSM have hindered the understanding of the full pathophysiology which would aid the development of new therapeutic avenues of investigation. Further elucidation of the role of ischemia, currently a source of debate, as well as the complex cascade of biomolecular events as a result of the unique pathophysiology in this disease will pave the way for further neuroprotective strategies to be developed to attenuate the physiological consequences of surgical decompression and augment its benefits.

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“…, 1, 2 CSM in dogs shares similarities with cervical spondylotic myelopathy, the most common cause of chronic compressive cervical myelopathy in people 2, 3, 4. While surgical treatment can attenuate the progression of this human disease, many patients are left with substantial neurologic disability 3.…”

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confidence: 99%

“…Gaps in the knowledge of the disease pathobiology have historically limited therapeutic advances in this human condition and current studies are actively investigating the disease pathogenesis with the objective of developing new neuroprotective approaches to improve outcome 3, 4, 5, 6, 7, 8, 9. Rodent models of cervical spondylotic myelopathy show that neuronal and oligodendrocyte apoptosis, chronic neuroinflammation, and microvascular compromise result in progressive neural degeneration and potentially irreversible spinal cord (SC) damage and could be related to treatment failure, poor long‐term outcome, or both 3, 4, 5, 6, 7, 8, 9. Similar changes have been observed in the SC of CSM‐affected dogs 2.…”

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confidence: 99%

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Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy

Martín-Vaquero

Costa

Moore

et al. 2014

Veterinary Internal Medicne

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BackgroundChronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs.Hypothesis/ObjectivesThat cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM‐affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)‐6 and monocyte chemoattractant protein‐1/chemokine ligand 2 (MCP‐1/CCL2).AnimalsClient‐owned GDs: 15 control, 15 CSM‐affected.MethodsProspective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti‐inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs.ResultsAffected GDs had significantly lower MCP‐1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85–161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68–260.11, P = .028). In affected GDs, MCP‐1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti‐inflammatory medications, disease duration, or disease severity. IL‐6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92–2.47, P < .001) in GDs with SC signal changes.Conclusions and Clinical ImportanceLower MCP‐1/CCL2 in CSM‐affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL‐6 in CSM‐affected GDs with SC signal changes suggests more severe inflammation in this group.

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A novel experimental model of cervical spondylotic myelopathy (CSM) to facilitate translational research

Cited by 113 publications

References 41 publications

Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Pathobiology of cervical spondylotic myelopathy

Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy

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