급성 척수 손상 쥐 모델에서 Statins과 Erythropoietin, Polyethylene Glycol 투여 후 행동 변화 및 조직학적 변화

Abstract

Purpose: To evaluate the neuroprotective effect of statins, erythropoietin and polyethylene glycol (PEG) after a spinal cord injury. Materials and Methods: Forty 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, 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 also underwent horizontal ladder test and sensory pin-prick test. The animals were sacrificed at the end of 6 weeks and a spinal cord specimen was harvested. 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 simvastatin and PEG-treated animals (p<0.05). There were no difference among four groups with the horizontal ladder test and pin-prick sensory test (p>0.05). There were no significant differences of gray matter sparing among four groups. The areas of white matter at the lesion epicenter were 0.78±0.05mm2, 0.46±0.04 mm2, 0.68±0.15 mm2, 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 neuroprotective effect after spinal cord injury in rats. and, they showed almost same efficacy. But, erythropoietin administration did not showed neuroprotective effect after spinal cord injury. To translate human trial from this study, further investigation is necessary about drug metabolism and pharmacokinetics of the drugs in the human body.