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Journal of Neurorestoratology 2017, 5(1): 21-29 https://doi.org/10.2147/JN.S123968
Original Research | Open Access | Issue | Published: 17 January 2017

Neurorestoratology evidence in an animal model with cervical spondylotic myelopathy

Show Author's Information Xiang Li1,2,  Guangsheng Li1,3,  Keith Dip-Kei Luk1,  Yong Hu1,2,3( )
Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong,
Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong-Shenzhen Hospital, Shenzhen,
Spinal Division, Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, Guangdong, People’s Republic of China
Keywords:
neurorestoratology, chronic spinal cord injury, cervical spondylotic myelopathy, surgical decompression, animal model
Cite this article:
Li X, Li G, Dip-Kei Luk K, et al. Neurorestoratology evidence in an animal model with cervical spondylotic myelopathy. Journal of Neurorestoratology, 2017, 5(1): 21-29. https://doi.org/10.2147/JN.S123968
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Abstract Full text About this article
Background:

Cervical spondylotic myelopathy (CSM) is a chronic compression injury of the spinal cord, with potentially reversible conditions after surgical decompression, and a unique model of incomplete spinal cord injury. Several animal studies showed pathological changes of demyelination, axon loss and neuron apoptosis in rats with chronic spinal cord compression. However, there is a limited understanding of the neurological change in the spinal cord after surgical decompression. The aim of this study was to validate the neurorestoratology of myelopathic lesions in the spinal cord in a rat model.

Materials and methods:

A total of 16 adult Sprague-Dawley rats were divided into four groups: sham control (group 1); CSM model with 4-week chronic compression (group 2), 2 weeks (group 3) and 4 weeks (group 4) after surgical decompression of CSM model. The compression and decompression were verified by magnetic resonance imaging (MRI) test. Neurological function was evaluated by Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, ladder rung walking test and somatosensory-evoked potentials (SEPs). Neuropathological change was evaluated by histological examinations.

Results:

MRI confirmed the compression of the cervical spinal cord as well as the reshaping of cord morphology after decompression. After decompression, significant changes of neurological function were observed in BBB scores (p < 0.01, F = 10.52), ladder rung walking test (p < 0.05, F = 14.21) and latencies (p < 0.05, F = 5.76) and amplitudes (p < 0.05, F = 3.8) of SEP. Neuronal degeneration was obvious in the ventral horn with gradual restoration. After decompression, the motor neuron number in the ventral horn did not show significant changes (p > 0.05). However, increasing trend of myelin area and staining intensity were observed in all columns of the white matter (p < 0.05) after decompression, especially in the compressed lateral column.

Conclusion:

The established rat model is able to simulate histopathological characteristics of cervical myelopathy in human beings. The neuropathological change demonstrated that neurorestoratology in the myelopathic spinal cord would probably attribute to axonal remyelination of the white matter, but there would be an incapability of neuronal regeneration.


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About this article

Neurorestoratology evidence in an animal model with cervical spondylotic myelopathy

Show Author's information Xiang Li1,2, Guangsheng Li1,3, Keith Dip-Kei Luk1, Yong Hu1,2,3( )
Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong,
Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong-Shenzhen Hospital, Shenzhen,
Spinal Division, Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, Guangdong, People’s Republic of China

Abstract

Background:

Cervical spondylotic myelopathy (CSM) is a chronic compression injury of the spinal cord, with potentially reversible conditions after surgical decompression, and a unique model of incomplete spinal cord injury. Several animal studies showed pathological changes of demyelination, axon loss and neuron apoptosis in rats with chronic spinal cord compression. However, there is a limited understanding of the neurological change in the spinal cord after surgical decompression. The aim of this study was to validate the neurorestoratology of myelopathic lesions in the spinal cord in a rat model.

Materials and methods:

A total of 16 adult Sprague-Dawley rats were divided into four groups: sham control (group 1); CSM model with 4-week chronic compression (group 2), 2 weeks (group 3) and 4 weeks (group 4) after surgical decompression of CSM model. The compression and decompression were verified by magnetic resonance imaging (MRI) test. Neurological function was evaluated by Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, ladder rung walking test and somatosensory-evoked potentials (SEPs). Neuropathological change was evaluated by histological examinations.

Results:

MRI confirmed the compression of the cervical spinal cord as well as the reshaping of cord morphology after decompression. After decompression, significant changes of neurological function were observed in BBB scores (p < 0.01, F = 10.52), ladder rung walking test (p < 0.05, F = 14.21) and latencies (p < 0.05, F = 5.76) and amplitudes (p < 0.05, F = 3.8) of SEP. Neuronal degeneration was obvious in the ventral horn with gradual restoration. After decompression, the motor neuron number in the ventral horn did not show significant changes (p > 0.05). However, increasing trend of myelin area and staining intensity were observed in all columns of the white matter (p < 0.05) after decompression, especially in the compressed lateral column.

Conclusion:

The established rat model is able to simulate histopathological characteristics of cervical myelopathy in human beings. The neuropathological change demonstrated that neurorestoratology in the myelopathic spinal cord would probably attribute to axonal remyelination of the white matter, but there would be an incapability of neuronal regeneration.

Keywords: neurorestoratology, chronic spinal cord injury, cervical spondylotic myelopathy, surgical decompression, animal model

References(35)

1.
Bilston LE, Thibault LE. The mechanical properties of the human cervical spinal cord in vitro. Ann Biomed Eng. 1996;24(1):67-74.
DOI Google Scholar
2.
Breig A. Overstretching of and circumscribed pathological tension in the spinal cord - a basic cause of symptoms in cord disorders. J Biomech. 1970;3(1):7-9.
DOI Google Scholar
3.
Breig A, Turnbull I, Hassler O. Effects of mechanical stresses on the spinal cord in cervical spondylosis. A study on fresh cadaver material. J Neurosurg. 1966;25(1):45-56.
DOI Google Scholar
4.
Henderson FC, Geddes JF, Crockard HA. Neuropathology of the brainstem and spinal cord in end stage rheumatoid arthritis: implications for treatment. Ann Rheum Dis. 1993;52(9):629-637.
DOI Google Scholar
5.
Smith CG. Changes in length and position of the segments of the spinal cord with changes in posture in the monkey. Radiology. 1956;66(2):259-266.
DOI Google Scholar
6.
Henderson FC, Geddes JF, Vaccaro AR, Woodard E, Berry KJ, Benzel EC. Stretch-associated injury in cervical spondylotic myelopathy: new concept and review. Neurosurgery. 2005;56(5):1101-1113.
Google Scholar
7.
Matsuda Y, Shibata T, Oki S, Kawatani Y, Mashima N, Oishi H. Outcomes of surgical treatment for cervical myelopathy in patients more than 75 years of age. Spine. 1999;24(6):529-534.
DOI Google Scholar
8.
Sampath P, Bendebba M, Davis JD, Ducker TB. Outcome of patients treated for cervical myelopathy. A prospective, multicenter study with independent clinical review. Spine. 2000;25(6):670-676.
DOI Google Scholar
9.
Ebersold MJ, Pare MC, Quast LM. Surgical treatment for cervical spondylitic myelopathy. J Neurosurg. 1995;82(5):745-751.
DOI Google Scholar
10.
Huang HY, Chen L. Neurorestorative process, law, and mechanisms. J Neurorestoratol. 2015;3:23-30.10.2147/JN.S74139
DOI Google Scholar
11.
Yamaura I, Yone K, Nakahara S, et al. Mechanism of destructive pathologic changes in the spinal cord under chronic mechanical compression. Spine. 2002;27(1):21-26.
DOI Google Scholar
12.
Baba H, Maezawa Y, Imura S, Kawahara N, Nakahashi K, Tomita K. Quantitative analysis of the spinal cord motoneuron under chronic compression: an experimental observation in the mouse. J Neurol. 1996;243(2):109-116.
DOI Google Scholar
13.
Crowe MJ, Bresnahan JC, Shuman SL, Masters JN, Beattie MS. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med. 1997;3(1):73-76.
DOI Google Scholar
14.
Fehlings MG, Skaf G. A review of the pathophysiology of cervical spondylotic myelopathy with insights for potential novel mechanisms drawn from traumatic spinal cord injury. Spine. 1998;23(24):2730-2737.
DOI Google Scholar
15.
Hu Y, Wen CY, Li TH, Cheung MM, Wu EX, Luk KD. Somatosensory-evoked potentials as an indicator for the extent of ultrastructural damage of the spinal cord after chronic compressive injuries in a rat model. Clin Neurophysiol. 2011;122(7):1440-1447.
DOI Google Scholar
16.
Long HQ, Li GS, Lin EJ, et al. Is the speed of chronic compression an important factor for chronic spinal cord injury rat model? Neurosci Lett. 2013;545:75-80.
DOI Google Scholar
17.
Karadimas SK, Moon ES, Yu WR, et al. A novel experimental model of cervical spondylotic myelopathy (CSM) to facilitate translational research. Neurobiol Dis. 2013;54:43-58.
DOI Google Scholar
18.
Gledhill RF, Harrison BM, McDonald WI. Demyelination and remyelination after acute spinal cord compression. Exp Neurol. 1973;38(3):472-487.
DOI Google Scholar
19.
Al-Mefty O, Harkey LH, Middleton TH, Smith RR, Fox JL. Myelopathic cervical spondylotic lesions demonstrated by magnetic resonance imaging. J Neurosurg. 1988;68(2):217-222.
DOI Google Scholar
20.
Hashizume Y, Iljima S, Kishimoto H, Hirano A. Pencil-shaped softening of the spinal cord. Pathologic study in 12 autopsy cases. Acta Neuropathol. 1983;61(3-4):219-224.
DOI Google Scholar
21.
Hashizume Y, Iijima S, Kishimoto H, Yanagi T. Pathology of spinal cord lesions caused by ossification of the posterior longitudinal ligament. Acta Neuropathol. 1984;63(2):123-130.
DOI Google Scholar
22.
Alafifi T, Kern R, Fehlings M. Clinical and MRI predictors of outcome after surgical intervention for cervical spondylotic myelopathy. J Neuroimaging. 2007;17(4):315-322.
DOI Google Scholar
23.
Beattie MS, Manley GT. Tight squeeze, slow burn: inflammation and the aetiology of cervical myelopathy. Brain. 2011;134(pt 5):1259-1261.
DOI Google Scholar
24.
Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1-21.
DOI Google Scholar
25.
Metz GA, Whishaw IQ. The ladder rung walking task: a scoring system and its practical application. J Vis Exp. 2009;28:e1204.
DOI Google Scholar
26.
Huang HY, Sharma HS. Neurorestoratology: one of the most promising new disciplines at the forefront of neuroscience and medicine. J Neurorestoratol. 2013;1:37-41.10.2147/JN.S47592
DOI Google Scholar
27.
Martinez M, Brezun JM, Bonnier L, Xerri C. A new rating scale for open-field evaluation of behavioral recovery after cervical spinal cord injury in rats. J Neurotrauma. 2009;26(7):1043-1053.
DOI Google Scholar
28.
Seyal M, Emerson RG, Pedley TA. Spinal and early scalp-recorded components of the somatosensory evoked potential following stimulation of the posterior tibial nerve. Electroencephalogr Clin Neurophysiol. 1983;55(3):320-330.
DOI Google Scholar
29.
Nakanishi T, Shimada Y, Sakuta M, Toyokura Y. The initial positive component of the scalp-recorded somatosensory evoked potential in normal subjects and in patients with neurological disorders. Electroencephalogr Clin Neurophysiol. 1978;45(1):26-34.
DOI Google Scholar
30.
Hu Y, Ding Y, Ruan D, Wong YW, Cheung KM, Luk KD. Prognostic value of somatosensory-evoked potentials in the surgical management of cervical spondylotic myelopathy. Spine. 2008;33(10):E305-E310.
DOI Google Scholar
31.
Johansson BB. Regeneration and plasticity in the brain and spinal cord. J Cereb Blood Flow Metab. 2007;27(8):1417-1430.
DOI Google Scholar
32.
Ek CJ, Habgood MD, Dennis R, et al. Pathological changes in the white matter after spinal contusion injury in the rat. PLoS One. 2012;7(8):e43484.
DOI Google Scholar
33.
Andrews RJ, Quintana L. Full spectrum neurorestoratology: enhancing neuroresponse to disasters. J Neurorestoratol. 2014;2:95-106.
DOI Google Scholar
34.
Grecco LLS, Michel S, Castillo-Saavedra L, Mourdoukoutas A, Bikson M, Felipe Fregni F. Transcutaneous spinal stimulation as a therapeutic strategy for spinal cord injury: state of the art. J Neurorestoratol. 2015;3:73-82.
DOI Google Scholar
35.
Enomoto M. Therapeutic effects of neurotrophic factors in experimental spinal cord injury models. J Neurorestoratol. 2016;4:15-22.
DOI Google Scholar
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Publication history

Published: 17 January 2017
Issue date: December 2017

Copyright

© 2017 The Author(s).

Acknowledgements

This study was supported by the National Natural Science Foundation of China (81572193), General Research Fund of the University Grant Council of Hong Kong (767511M), Shenzhen Knowledge Innovation Program of Basic Research Items of Guangdong Province (JCYJ20150331142757393) and Natural Science Foundation of Guangdong Province, China (2016A030313679).

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