Recombinant DNA vaccine against inhibition of neurite outgrowth promotes functional recovery associated with endogeous NGF expression in spinal cord hemisected adult rats.
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.
Zhang
Yi
Y
Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu, China.
Hao
Chun-Guang
CG
Hu
Li-Qun
LQ
Dong
Jian
J
Wei
Peng
P
Xu
Dan
D
Xiao
Zhi-Cheng
ZC
Wang
Ting-Hua
TH