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Neuroprotective Effects of PEP-1-Cu,Zn-SOD against Ischemic Neuronal Damage in the Rabbit Spinal Cord

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Abstract

A rabbit model of spinal cord ischemia has been introduced as a good model to investigate the pathophysiology of ischemia–reperfusion (I–R)-induced paraplegia. In the present study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) against ischemic damage in the ventral horn of L5–6 levels in the rabbit spinal cord. For this study, the expression vector PEP-1 was constructed, and this vector was fused with SOD1 to create a PEP-1-SOD1 fusion protein that easily penetrated the blood–brain barrier. Spinal cord ischemia was induced by transient occlusion of the abdominal aorta for 15 min. PEP-1-SOD1 (0.5 mg/kg) was intraperitoneally administered to rabbits 30 min before ischemic surgery. The administration of PEP-1-SOD1 significantly improved neurological scores compared to those in the PEP-1 (vehicle)-treated ischemia group. Also, in this group, the number of cresyl violet-positive cells at 72 h after I–R was much higher than that in the vehicle-treated ischemia group. Malondialdehyde levels were significantly decreased in the ischemic spinal cord of the PEP-1-SOD1-treated ischemia group compared to those in the vehicle-treated ischemia group. In contrast, the administration of PEP-1-SOD1 significantly ameliorated the ischemia–induced reduction of SOD and catalase levels in the ischemic spinal cord. These results suggest that PEP-1-SOD1 protects neurons from spinal ischemic damage by decreasing lipid peroxidation and maintaining SOD and catalase levels in the ischemic rabbit spinal cord.

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Acknowledgments

The authors would like to thank Mr. Seok Han, Mr. Seung Uk Lee and Ms. Hyun Sook Kim for their technical help in this study. This work was supported by a grant no. 01-2006-04 from the Hallym University Medical Center Research Fund.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Woosuk Kim, Dae Young Yoo & In Koo Hwang

  2. Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 200-702, South Korea

    Dae Won Kim & Soo Young Choi

  3. Department of Neurology, Seoul National University Hospital, Seoul, 110-744, South Korea

    Jin Young Chung

  4. Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Moo-Ho Won

  5. Department of Neurosurgery, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, 150-719, South Korea

    Sei Woong Jeon, Je Hoon Jeong, Hyung Sik Hwang & Seung Myung Moon

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  1. Woosuk Kim
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Correspondence to Seung Myung Moon.

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11064_2011_613_MOESM1_ESM.tif

Supplementary material 1 (TIFF 12371 kb). Neurological function scores by modified Tarlov criteria in the sham, PEP-1-ischemia and PEP-1-SOD1-ischemia groups at 24, 48, and 72 h after I-R

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Kim, W., Kim, D.W., Yoo, D.Y. et al. Neuroprotective Effects of PEP-1-Cu,Zn-SOD against Ischemic Neuronal Damage in the Rabbit Spinal Cord. Neurochem Res 37, 307–313 (2012). https://doi.org/10.1007/s11064-011-0613-0

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  • DOI: https://doi.org/10.1007/s11064-011-0613-0

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