Oral Presentation 6th Australian Health and Medical Research Congress 2012

Anit-proBDNF antibody promotes axonal regeneration after spinal cord injury (#144)

Ying (Annie) Sun 1 , Rainer Haberberger 2 , Xin-Fu Zhou* 1
  1. Sansom Institute, University of South Australia, Adelaide , SA, Australia
  2. Department of Anatomy & Histology, Centre for Neuroscience, Flinders University, Adelaide, SA, Australia

Background: After sciatic nerve conditioning lesion and spinal cord injury, brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are increased in both the dorsal root ganglia (DRG) and spinal cord. BDNF plays a critical role in the enhanced regeneration of spinal cord following conditioning lesion of sciatic nerve but the function of proBDNF in the injured spinal cord is not known. In the present study we have examined whether the anti-proBDNF antibody can promote nerve regeneration after spinal cord injury. Methodology: Following sciatic nerve transection for a week, the dorsal column hemisection of the spinal cord were undergone at T9 in female rats. Injured rats were treated with anti-proBDNF antibody or normal sheep IgG via Alzet pumps implanted on the injury sites for two weeks. DRG sensory neurons were labelled with retrograde tracer fast blue (FB) injected at T8 and anterograde tracer biotin dextran amine (BDA) at L4. Results: After conditioning lesion, the number of FB-labelled neurons in the ipsilateral DRG (27.7 ± 3.5/section) of the anti-proBDNF antibody-treated rats was significantly higher than that in the contralateral side (7.2 ± 1.9/section) and ipsilateral DRG of rats treated with IgG both sides (12.9 ± 1.1/section, 2.8 ± 0.5/section, n = 5 rats/group, p < 0.05). In the anti-proBDNF antibody treated rats the ascending fibers labelled by BDA approached the injury site and regenerative sprouts were interrupted by the scar. Many labelled fibers bypass the lesion site through the ventral gray matter. Branching of regenerating axons into the gray matter and terminal arborization indicates the establishment of connections to local spinal neurons. However, in the rats treated with IgG, the injury-induced sprouts occurred caudal to the lesion but failed to elongate over long distances. Conclusions: The inhibition of endogenous proBDNF establishes more favourable conditions for the regeneration of injured sensory neurons. Anti-proBDNF treatment may have therapeutic potential for the injured central nervous system.