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Macrophages contribute to the maintenance of stable regenerating neurites following peripheral nerve injury
Author(s) -
Luk Hoenie W.,
Noble Linda J.,
Werb Zena
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10701
Subject(s) - sciatic nerve , neurite , wallerian degeneration , regeneration (biology) , peripheral nerve injury , nerve injury , anatomy , peripheral nervous system , peripheral nerve , sciatic nerve injury , microbiology and biotechnology , schwann cell , pathology , biology , neuroscience , chemistry , medicine , central nervous system , in vitro , biochemistry
Normal adult uninjured nerve is unable to support axonal regeneration. We have studied the mechanisms underlying the regeneration of peripheral nerve by culturing adult mouse dorsal root ganglia (DRG) explants on unfixed, longitudinal cryosections of either the uninjured sciatic nerve or the distal segment of the transected sciatic nerve. We found that, initially, DRG grew vigorously on cryosections of both uninjured and postinjury sciatic nerves. However, the neurites began to degenerate shortly after contact with the uninjured nerve, whereas those growing on postinjury nerve substrate remained healthy for up to 9 days in culture. This ability to support stable outgrowth peaked at 8 days, gradually decreased by 10 days, and disappeared by 20 days after injury. Macrophages appeared in the distal segment by 4 days postinjury and had infiltrated its entire length by 8 days. Uninjured nerve cryosections could be rendered supportive of stable outgrowth by preincubation with macrophage‐conditioned medium or by brief trypsinization. The activity of the macrophage‐conditioned medium was augmented upon activation of macrophages. Together these findings suggest that the environment of the sciatic nerve undergoes a transformation during Wallerian degeneration such that it becomes transiently supportive of the stable outgrowth of neurites. This transformation may be mediated by a proteolytic activity, generated by activated macrophages, that removes a putative “degeneration signal” protein normally present in the adult nerve and thus contributes to the maintenance of stable regenerating neurites. © 2003 Wiley‐Liss, Inc.