Published online Sep 30, 2012.
https://doi.org/10.4184/jkss.2012.19.3.77
Diminution of Secondary Injury after Administration of Pharmacologic Agents in Acute Spinal Cord Injury Rat Model -Comparison of Statins, Erythropoietin and Polyethylene Glycol-
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.
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 improved 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 improved 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 animals 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.
References
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