ProBDNF inhibits infiltration of ED1+ macrophages after spinal cord injury
The central nervous system (CNS) does not regenerate partly due to the slow clearance of debris from the degenerated myelin sheath by Wallerian degeneration. The mechanism underlying the inefficiency in myelin clearance is not clear. Here we showed that endogenous proBDNF may inhibit the infiltration of ED1+ inflammatory cells afterspinalcordinjury. Afterinjury, proBDNF and its receptors sortilin and p75NTR are expressed in the spinalcord as determined by Western blots and immunocytochemistry. ProBDNF and mature BDNF were released from macrophagesin vitro. Macrophagesin vivo (ED1+) and isolated in vitro (CD11b+) express moderate levels of proBDNF, sortilin and p75NTR. ProBDNF suppressed the migration of isolated macrophagesin vitro and the antibody to proBDNF enhanced the migration. Suppression of proBDNFin vivo by administering the antiserum to the prodomain of BDNF afterspinalcordinjury (SCI) increased the infiltration of macrophages and increased number of neurons in the injured cord. BBB tests showed that the treatment of the antibody to proBDNF improved the functional recovery afterspinalcordinjury. Our data suggest that proBDNF is a suppressing factor for macrophage migration and infiltration and may play a detrimental role after SCI.
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