Development and Characterization of a Novel Rat Model of Cervical Spondylotic Myelopathy: The Impact of Chronic Cord Compression on Clinical, Neuroanatomical, and Neurophysiological Outcomes

Abstract

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord impairment worldwide and is a risk factor for traumatic central cord syndrome. Despite advances in surgery, there are no effective neuroprotective treatments for CSM, which reflects a limited understanding of its pathophysiology. In order to develop therapeutic strategies, we have developed a novel rat model of chronic progressive cervical spinal cord compression that mimics CSM. A titanium-screw-based chronic compression device (CCD) was designed to achieve progressive cord compression at the C6 level. The CCD was fixed to the C2 and T2 spinous processes and a threaded screw was turned to induce compression. Sprague-Dawley rats (n=75) were divided into three groups: (1) sham (no compression, n=6), (2) mild compression (1.4 mm stenosis, n=27), and (3) severe compression (2.6 mm stenosis, n=42). Compression was evaluated using micro-computed tomography (micro-CT). The area of spared white matter, extent of cord flattening ratio, and loss of neurons were assessed. Functional deficits were characterized using sensory-evoked potential (SEP) recordings, and with neurobehavioral tests: the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, inclined plane, paw grip strength, and assessment of mechanical and thermal allodynia. Micro-CT confirmed progressive canal stenosis. The loss of intact white matter and cord flattening were significantly greater in rats with severe cord compression, and the number of neurons was reduced at the epicenter of cord compression. With chronic cord compression there was a significant decline in locomotor function, forelimb function, trunk stability/coordination, an increase in mechanical allodynia, and impaired axonal conduction. The CCD model results in chronic and precise cervical cord compression. The compression is associated with mechanical allodynia and measurable neurobehavioral, neurophysiological, and neuropathological deficits. We anticipate that the CCD model will enable the investigation of translationally-relevant therapeutic strategies for CSM.

Is the speed of chronic compression an important factor for chronic spinal cord injury rat model?

“…Development of appropriate experimental chronic spinal cord injury animal models is crucial for investigating the pathophysiological mechanisms of CSM [10]. In previous studies, chronic compression spinal cord injury rat models were developed using a modified water absorption polyurethane material with different expansion speeds [3,5,15].…”

Recombinant human bone morphogenetic protein-2–induced ossification of the ligamentum flavum in rats and the associated global modification of histone H3

“…The normal canal anteroposterior diameter was measured at the midvertebral body level. The following equation was used to quantify the maximum compression ratio: 15 where D is the anteroposterior canal diameter at the level of maximum protrusion, Du is the anteroposterior canal diameter at the nearest normal level above the level of operation, and Dd is the anteroposterior canal diameter at the nearest normal level below the level of operation.…”

Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy

“…Existing models mimicking chronic cord compression in rats include insertion of expandable polymers [50], adjustable screws [33], and calcification-inducing polymers [28]. These result in loss of neurons, predominantly in the grey matter of the ventral horns at the lesion epicentre.…”