Recombinant DNA Vaccine Against Inhibition of Neurite Outgrowth Promotes Functional Recovery Associated with Endogeous NGF Expression in Spinal Cord Hemisected Adult Rats |
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Authors: | Yi Zhang Chun-Guang Hao Li-Qun Hu Jian Dong Peng Wei Dan Xu Zhi-Cheng Xiao Ting-Hua Wang |
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Institution: | (1) Institute of Neurological Disease, West China Hospital, Sichuan University, 610041 Chengdu, China;(2) Institute of Neuroscience, Kunming Medical College, No. 191, Renmin Western Road, 650031 Kunming, China;(3) Cadre’s Ward, Anhui Provincial Hospital, 230001 Hefei, China;(4) Department of Biotherapy Center, No 1 Affiliated Hospital, Kunming Medical College, 650032 Kunming, China;(5) Department of Clinical Research, Singapore General Hospital, Singapore, Singapore |
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Abstract: | Axonal regeneration across the site of spinal cord lesion is often aborted in adult mammalian species. The use of DNA vaccine
to nullify the inhibitory molecules has been shown to be effective in promoting axonal regeneration in injured spinal cord.
The possible molecular mechanisms, however, remain to be elucidated. The present study showed that the administration of recombinant
DNA vaccine encoding multiple domains, Nogo-66, Nogo-N, TnR, and MAG, significantly improved hindlimb locomotor functions
in rats subjected to ablation of the dorsal halves of the cord. Western blot analysis demonstrated that nerve growth factor
(NGF) levels in the spinal cord of immunized rats were significantly upregulated than those of control rats. Immunohistochemistry
as well as in situ hybridization confirmed that NGF was expressed in neurons of the spinal cord. These findings indicated
that functional recovery in immunized rats could be correlated with endogeous NGF expression in hemisected rat spinal cords.
Y. Zhang and C.-G. Hao contributed equally to this work. |
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Keywords: | DNA vaccine Hemisected spinal cord NGF Rat |
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