RETRACTED ARTICLE: Therapeutic DNA Vaccination as a Repair Strategy Following Spinal Cord Injury |
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Authors: | Sheng-Bin Kou Gang Xu Xiao-Dan Jiang Ru-Xiang Xu Yan-Ping Tang Gang Xu Ying-Qian Cai Mou-Xuan Du Zhi-Cheng Xiao |
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Institution: | (1) Neurosurgery Institute of Guangdong, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, 253# Gongye Road, 510282 Guangzhou, People’s Republic of China;(2) Institute of Molecular and Clinical Medicine, Kunming Medical College, Kunming City, China;(3) R&D China, GlaxoSmithKline, Shanghai, China;(4) Department of Neurosurgery, The Military General Hospital of Beijing PLA., 100700 Beijing, People’s Republic of China;(5) Department of Neurosurgery, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; |
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Abstract: | Myelin-derived proteins, such as tenascin-R (TN-R), myelin associate glycoprotein (MAG), oligodendrocyte-myelin glycoprotein
(OMgp), and Nogo-A, inhibit the central nervous system regeneration. In this study, the DNA vaccine encoding for oligodendrocyte
and myelin-related antigens was employed to attenuate the axonal growth inhibitory properties of myelin in the setting of
spinal cord injury. Using a rat spinal cord dorsal hemisection model, the vaccine directed against the inhibitory epitopes
of Nogo-A, MAG, OMgp, and TN-R was administered intramuscularly once a week following spinal cord injury, supplemented with
local application of specific anti-sera against the four antigens. Anterograde labeling of dorsal column fibers showed active
axonal regeneration through the lesion site at the eighth week following the treatment in experimental group but not in control
groups. Light microscopic and ultrastructural analysis revealed that vaccination with these myelin-related antigens did not
lead to demyelinating disease. OMgp and TN-R levels were down-regulated at the lesion site together with a parallel increase
in growth-associated protein 43 levels in the treatment groups. This study reveals the effective approach of a DNA vaccine
strategy by attaining the special antibody to direct neutralization of the myelin inhibitors during spinal cord injury. |
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