J Korean Orthop Assoc.  2008 Oct;43(5):551-559. 10.4055/jkoa.2008.43.5.551.

Neuroprotection for Acute Spinal Cord Injury: Comparison of Simvastatin and Atorvastatin

• Lee JY
• Sohn HM
• You JW
• Yang KH
• Nam KY
• Kwon BK

• KMID: 2186415
• DOI: http://doi.org/10.4055/jkoa.2008.43.5.551

Abstract

PURPOSE: To evaluate the neuroprotective effect of statins after a spinal cord injury.
MATERIALS AND METHODS
Twenty four Sprague Dawley rats had a spinal cord injury at T9/10 using an Ohio State University (OSU) impactor. The animals were randomized to receive either simvastatin, atorvastatin, or saline with oral gavage everyday for 7 days. 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 also underwent sensory threshold testing using a von Frey monofilament device. The animals were sacrificed at the end of 6 weeks and a spinal cord specimen was harvested. Histology and immunohistochemistry were performed to measure the areas of white and gray matter, and the sparing of oligodenrocytes.
RESULTS
For the animals treated with simvastatin, atorvastatin and saline, the mean BBB scores at 6 weeks post-injury was 13.2+/-0.1, 11.8+/-0.5, and 11.3+/-0.2 and the BBB subscores were 9.2+/-1.1, 4.8+/-1.8 and 4.4+/-1.4 respectively (p<0.05). The areas of white matter at the lesion epicenter were 0.78+/-0.05, 0.5+/-0.18 and 0.41+/-0.03 mm2 in the simvastatin, atorvastatin and saline groups respectively, and the number of spared oligodendrocytes was significantly higher in the simvastatin treated animals (p<0.05).
CONCLUSION
The simvastatin treatment improved the behavior and histological sparing of the spinal cord after an acute spinal cord injury in rats.

Keyword

Acute spinal cord injury; Neuroprotection; Simvastatin; Atorvastatin

MeSH Terms

Animals
Heptanoic Acids
Humans
Immunohistochemistry
Neuroprotective Agents
Ohio
Oligodendroglia
Pyrroles
Rats, Sprague-Dawley
Sensory Thresholds
Simvastatin
Spinal Cord
Spinal Cord Injuries
Atorvastatin Calcium
Heptanoic Acids
Neuroprotective Agents
Pyrroles
Simvastatin

Figure

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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 a 1.5 mm displacement injury at 300 m/s.

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  Fig. 2 (A) BBB score. The simvastatin-treated animals showed improved open-field locomotor (BBB) scores compared with the control or atorvastatin-treated animals (*p<0.05). (B) BBB subscore. The simvastatin-treated animals showed improved BBB subscores compared with the control or atorvastatin-treated animals (*p<0.05).

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  Fig. 3 Histology assessment. The simvastatin-treated animals showed increased sparing of the white matter at the injury epicenter and at 0.4 mm rostral and 0.2 mm caudal (*p<0.05).

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  Fig. 4 Immunohistochemistry staining. The simvastatin-treated animals showed significantly higher numbers of oligodendrocytes (as stained by Hoechst 33258 and CC1 immunohistochemistry, blue) compared with both the atorvastatin and control animals (*p<0.05).

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  Fig. 5 Immunohistochemistry staining. The ratio of caspase-3 positive oligodendrocytes (green) was significantly lower in the simvastatin-treated animals compared with both the atorvastatin and control animals, which is indicative of reduced apoptotic death (*p<0.05).

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