Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

A novel experimental model of cervical spondylotic myelopathy (CSM) to facilitate translational research. Neurobiol Dis 2013 Jun;54:43-58

Date

03/08/2013

Pubmed ID

23466695

DOI

10.1016/j.nbd.2013.02.013

Scopus ID

2-s2.0-84875333402   86 Citations

Abstract

Cervical spondylotic myelopathy (CSM) is the most common form of spinal cord impairment in adults. However critical gaps in our knowledge of the pathobiology of this disease have limited therapeutic advances. To facilitate progress in the field of regenerative medicine for CSM, we have developed a unique, clinically relevant model of CSM in rats. To model CSM, a piece of synthetic aromatic polyether, to promote local calcification, was implanted microsurgically under the C6 lamina in rats. We included a sham group in which the material was removed 30s after the implantation. MRI confirmed postero-anterior cervical spinal cord compression at the C6 level. Rats modeling CSM demonstrated insidious development of a broad-based, ataxic, spastic gait, forelimb weakness and sensory changes. No neurological deficits were noted in the sham group during the course of the study. Spasticity of the lower extremities was confirmed by a significantly greater H/M ratio in CSM rats in H reflex recordings compared to sham. Rats in the compression group experienced significant gray and white matter loss, astrogliosis, anterior horn cell loss and degeneration of the corticospinal tract. Moreover, chronic progressive posterior compression of the cervical spinal cord resulted in compromise of the spinal cord microvasculature, blood-spinal cord barrier disruption, inflammation and activation of apoptotic signaling pathways in neurons and oligodendrocytes. Finally, CSM rats were successfully subjected to decompressive surgery as confirmed by MRI. In summary, this novel rat CSM model reproduces the chronic and progressive nature of human CSM, produces neurological deficits and neuropathological features accurately mimicking the human condition, is MRI compatible and importantly, allows for surgical decompression.

Author List

Karadimas SK, Moon ES, Yu WR, Satkunendrarajah K, Kallitsis JK, Gatzounis G, Fehlings MG

Author

Kajana Satkunendrarajah PhD Assistant Professor in the Neurosurgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Cervical Vertebrae
Disease Models, Animal
Female
Immunohistochemistry
In Situ Nick-End Labeling
Rats
Rats, Sprague-Dawley
Spinal Cord Compression
Spinal Cord Diseases
Spondylosis