ABSTRACT
Objective To observe whether immature Brain Derived Neurotrophic Factor (proBDNF)can affect the activities of OPCs in the fields of cell proliferation and migration after SCI,and to investigate the relationship between proBDNF and p75NTR signal pathway on OPCs.Methods OLN-93 cell line was cultured and maintained for in vitro experiments.Immunofluorescence were used to check the expression of endogenous proBDNF,p75NTR and sortilin on OPCs.MTT assay was used to illustrate the inhibitory effect of proBDNF.The effects of anti-proBDNF was also observed by BrdU staining to find a probably signal pathway for proBDNF on OPCs.The Sprague-Dawley rats were administered for T9 spinal cord injury animal model.BBB score was applied to observe the situation of functional recovery after treated by anti-proBDNF.BrdU staining was managed to observe the situation of OPCs proliferation and migration after SCI.Results Endogenous proBDNF inhibited proliferation and migration of OPCs after SCI.BrdU staining showed that population of proliferative OPCs in lesion site of spinal cord was less in proBDNF in treated group than that in control group and anti-proBDNF group.While anti-proBDNF could inhibit proBDNF specifically and might induced a better functional recovery which was illustrated by BBB scores.The in vitro experiments found the inhibitory effect of proBDNF is dose-dependent and can be neutralized by anti-proBDNF properly.Moreover,the expression levels of p75NTR and sortilin are down regulated by proBDNF antibody treated group.This indicated that proBDNF may inhibit OPCs via p75NTR pathway.Conclusion Endogenous proBDNF can inhibit cell proliferation of OPCs after SCI and can be neutralized by specific antibodies of proBDNF.This kind of detrimental effect may be induced by p75NTR-sortilin pathway.Furthermore,proBDNF antibody treatment is effective to block proBDNF and promote the functional recovery.