Immunization with recombinant Nogo-66 receptor (NgR) promotes axonal regeneration and recovery of function after spinal cord injury in rats

Panpan Yu; Lidong Huang; Jian Zou; Zhihua Yu; Yanxia Wang; Xiaofei Wang; Liang Xu; Xinqiu Liu; Xiao-Ming Xu; Pei-Hua Lu

Neurobiology of Disease (Dec 2008)

Immunization with recombinant Nogo-66 receptor (NgR) promotes axonal regeneration and recovery of function after spinal cord injury in rats

Panpan Yu,
Lidong Huang,
Jian Zou,
Zhihua Yu,
Yanxia Wang,
Xiaofei Wang,
Liang Xu,
Xinqiu Liu,
Xiao-Ming Xu,
Pei-Hua Lu

Affiliations

Panpan Yu: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Lidong Huang: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Jian Zou: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Zhihua Yu: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Yanxia Wang: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Xiaofei Wang: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Liang Xu: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Xinqiu Liu: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Xiao-Ming Xu: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China; Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Corresponding authors. P.-H. Lu is to be contacted at Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, 280 South Chong-Qing Road, Shanghai 200025, China. Fax: +86 21 64453296; X.-M. Xu, Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Pei-Hua Lu: Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China; Corresponding authors. P.-H. Lu is to be contacted at Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, 280 South Chong-Qing Road, Shanghai 200025, China. Fax: +86 21 64453296; X.-M. Xu, Department of Neurobiology, Shanghai Jiaotong University, School of Medicine, Shanghai, China.

Journal volume & issue: Vol. 32, no. 3
pp. 535 – 542

Abstract

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Nogo-66 receptor (NgR), a common receptor for the three known myelin-associated inhibitors, i.e., Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), plays a key role in the failure of axonal regeneration in the adult mammalian central nervous system (CNS). Here we report a novel vaccine approach that stimulates the production of anti-NgR antibody to overcome NgR-mediated growth inhibition after spinal cord injury (SCI). We showed that adult rats immunized with recombinant NgR produced high titers of the anti-NgR antibody and that antisera obtained from the immunized rats promoted neurite outgrowth of rat cerebellar neurons on the inhibitory MAG substrate in vitro. In a spinal cord dorsal hemisection model, NgR immunization promoted regeneration of lesioned corticospinal tract (CST) axons, anterogradely labeled with biotin dextran amine (BDA), beyond the lesion site. In a contusive SCI model, NgR immunization markedly reduced the total lesion volume and improved Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and grid walking performance. Thus, the NgR vaccine approach may represent a promising repair strategy to promote structural and functional recovery following SCI.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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