The Neuroprotective Effect of Combination Therapy of Polyethylene Glycol and Magnesium Sulfate in Acute Spinal Cord Injury

Jun-Young Lee; Jae-Won You; Hong-Moon Sohn; Sang-Jun Lee; Brian K Kwon

doi:10.4055/jkoa.2009.44.4.414

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Lee, You, Sohn, Lee, and Kwon: The Neuroprotective Effect of Combination Therapy of Polyethylene Glycol and Magnesium Sulfate in Acute Spinal Cord Injury

Original Article

Journal of the Korean Orthopaedic Association

Journal of the Korean Orthopaedic Association 2009; 44(4): 414-421.

Published online: 21 July 2009

DOI: https://doi.org/10.4055/jkoa.2009.44.4.414

The Neuroprotective Effect of Combination Therapy of Polyethylene Glycol and Magnesium Sulfate in Acute Spinal Cord Injury

Jun-Young Lee, M.D., Jae-Won You, M.D., Hong-Moon Sohn, M.D., Sang-Jun Lee, M.D., Brian K Kwon, M.D.^*

Department of Orthopaedic Surgery, College of Medicine, Chosun University, Gwangju, Korea.

^*Combined Neurosurgical and Orthopaedic Spine Program, Department of Orthopaedics, University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada.

Correspondence to 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, hmsohn@chosun.ac.kr

Received 10 February 2009 Accepted 19 May 2009

Abstract

Purpose

To evaluate the neuroprotective effect of combination therapy of polyethylene glycol (PEG) and magnesium sulfate (MgSO₄) after a spinal cord injury.

Materials and Methods

Twenty Sprague Dawley male rats (300-350 gm) had a spinal cord injury after T9/10 laminectomy using an Ohio State University (OSU) impactor under intraperitoneal anesthesia. The animals were randomized to receive either PEG (1 g/kg)+MgSO₄ (300 mg/kg) or saline (2 ml) via carotid vein after 2 hours of injury and then every 6 hours for 5 times. The behavioral outcome assessments were performed on days 2, 4 and 7, and then every week using the Basso, Bresnahan, and Beattie (BBB) score and subscore. The animals also underwent sensory threshold testing using a von Frey monofilament device and gait analysis with Catwalk program before and 6 weeks after cord injury. 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 PEG+MgSO₄ and saline, the mean BBB scores at 6 weeks post-injury were 13.3±0.3, 11.4±0.2 and the BBB subscores were 9.1±1.1, 4.4±1.2 respectively (p<0.05). No significant differences were found in sensory testing and gait analysis between the two groups. Histologic assessment revealed no significant difference in gray matter sparing but the areas of white matter at the lesion epicenter were 0.68±0.2, 0.41±0.04 mm² in the PEG+MgSO₄ and saline groups respectively, which indicated significant sparing of white matter in PEG+MgSO₄ group (p<0.05).

Conclusion

The combination therapy of polyethylene glycol and magnesium sulfate improved the motor function and showed significant histological sparing of the spinal cord after an acute spinal cord injury in rats.

Keywords: Acute spinal cord injury, Polyethylen glycol, Magnesium sulfate

Figures and Tables

Fig. 1

Administration of PEG+MgSO₄ using port system. Injected pharmacologic agent is administrated to blood via external carotid vein.

Fig. 2

Foot prints (A-C) and gait diagram (D) using Catwalk program. (A) Forepaws only, (B) Hindpaws only, (C) All four paws combined. Regularity index, base of support, swing duration and stride length were measured.

Fig. 3

(A) BBB score. The PEG+MgSO₄-treated animals showed improved open-field locomotor (BBB) scores compared with the control animals (^*, p<0.05). (B) BBB subscore. The PEG+MgSO₄-treated animals showed improved BBB subscores compared with the control animals (^*, p<0.05).

Fig. 4

Pinprick sensory test. There was no significant difference between the two groups after 6 weeks post-injury (p>0.05).

Fig. 5

Histology assessment. There was no significant difference of grey matter sparing between the two groups. The PEG+MgSO₄-treated animals showed increased sparing of the white matter at the injury epicenter and at 0.2 mm rostral and 0.2 mm caudal (^*, p<0.05).

Table 1

Biomechanical Parameters of the Contusion Injury

There were no significant differences between the two groups with respect to the peak force of the injury and the displacement of the impactor tip.

Table 2

The Results of Gait Analysis

All parameters of gait analysis showed no significant differences between the two groups (p>0.05). ^*RI, Regularity index; ^†BOS, Base of support.

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