Diminution of Secondary Injury after Administration of Pharmacologic Agents in Acute Spinal Cord Injury Rat Model -Comparison of Statins, Erythropoietin and Polyethylene Glycol-

Jae-Won You; Hong-Moon Sohn; Sang-Ha Park

doi:10.4184/JKSS.2021.19.3.77

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You, Sohn, and Park: Diminution of Secondary Injury after Administration of Pharmacologic Agents in Acute Spinal Cord Injury Rat Model -Comparison of Statins, Erythropoietin and Polyethylene Glycol-

Original Research

J Korean Soc Spine Surg 2012;19(3):77-84.

Published online: 18 September 2012

DOI: https://doi.org/10.4184/JKSS.2021.19.3.77

Diminution of Secondary Injury after Administration of Pharmacologic Agents in Acute Spinal Cord Injury Rat Model -Comparison of Statins, Erythropoietin and Polyethylene Glycol-

Jae-Won You, M.D., Hong-Moon Sohn, M.D., Sang-Ha Park, M.D.

Department of Orthopaedic Surgery, School of Medicine, Chosun University, Gwangju, Korea

Corresponding author: Hong-Moon Sohn, M.D. Department of Orthopaedic Surgery, Chosun University Hospital, 588 Seosuk-Dong, Dong-Gu, Gwangju 501-717, Korea TEL: 82-62-220-3147, FAX: 82-62-226-3379 E-mail: hmsohn@chosun.ac.kr

Received 13 March 20121 June 2012 Accepted 7 June 2012

“This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.”

Abstract

Study Design

An experimental animal study.

Objectives

To evaluate and compare the neuroprotective effect of statins, erythropoietin and polyethylene glycol (PEG) after spinal cord injury (SCI).

Summary of Literature Review

There are few comparative studies of pharmacological agents for acute SCI.

Materials and Methods

Forty Sprague Dawley (SD) rats had a spinal cord injury at T9/10 using an Ohio State University (OSU) impactor. The animals were randomized to receive one of the following; simvastatin, erythropoietin, PEG or saline. A behavioral outcome assessment was performed on days 2, 4 and 7, and then every week using the Basso, Bresnahan, and Beattie (BBB) score and subscore. The animals were sacrificed at the end of 6 weeks and histologic assessment was performed to measure the areas of white and gray matter.

Results

For the animals treated with simvastatin, erythropoietin, PEG and saline, the mean BBB scores at 6 weeks post-injury were 13.2±0.1, 11.7±0.4, 13.3±0.3, and 11.4±0.2, and the BBB subscores were 9.2±1.1, 5.0±1.3, 9.1±1.1, 4.4±1.2, respectively. The BBB scores and BBB subscores were significantly higher in simvastain and PEG-treated animals (p<0.05). The areas of white matter at the lesion epicenter were 0.78±0.05mm², 0.46±0.04 mm², 0.68±0.15 mm², and 0.41±0.04mm² in the simvastatin, erythropoietin, PEG and saline groups, respectively. The simvastatin and PEG-treated animals showed increased sparing of the white matter at the injury epicenter and at 0.2mm rostral and 0.4mm caudal(p<0.05).

Conclusion

Simvastatin and polyethylene glycol administration showed diminished secondary injury after SCI in rats. In addition, they showed almost the same efficacy. However, erythropoietin did not show neuroprotective effect.

Keywords: Acute spinal cord injury, Statins, Erythropoietin, Polyethylene glycol, Rat

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Fig. 1.

Ohio State University (OSU) Impactor. A laminectomy (T9-10) was performed, and the bases of the adjacent spinous processes were secured with modified Allis clamps. The impactor was then triggered to deliver mechanical injury. Animal model of acute spinal cord contusion was made.

Fig. 2.

BBB score. Simvastatin and PEG-treated animals showed im-proved open-field locomotor (BBB) scores compared with erythropoietin and saline-treated control animals (∗, p<0.05).

Fig. 3.

BBB subscore. Simvastatin and PEG-treated animals showed im-proved BBB subscores compared with erythropoietin and saline-treated control animals (∗, p<0.05).

Fig. 4.

Horizontal ladder test. Comparing with preinjury, four groups showed increased hindlimb stepping errors. There was no difference among the four groups after 6 weeks post injury (p>0.05).

Fig. 5.

Pinprick sensory test. There was no difference among the four groups after 6 weeks post injury (p>0.05).

Fig. 6.

Histology assessment. There was no significant difference of gray matter sparing among the four groups. The simvastatin and PEG-treated ani-mals showed increased sparing of the white matter at the injury epicenter and at 0.2mm rostral and 0.4mm caudal(∗, p<0.05).

Table 1.

Biomechanical parameters of the contusion injury. There were no significant differences among the four groups with respect to the peak force of the injury and the displacement of the impactor tip.

Groups	Force (kdynes)	Displacement(mm)	n
Simvastatin	227 ± 5.24	1.46 ± 0.03	10
Erythropoietin	225 ± 4.72	1.46 ± 0.03	10
Polyethylene glycol	226 ± 6.74	1.46 ± 0.03	10
Control	226 ± 6.32	1.46 ± 0.03	10

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