Macrophages Hinder Regeneration

In contrast to Barrette et al., Horn al. report that macrophages may hinder regeneration in the spinal cord of rats by promoting axonal retraction. Central nervous system axons normally retract from a site of injury. To examine the role of macrophages in this process, Horn et al. specifically targeted phagocytic cells with toxin enclosed in liposomes. Depleting macrophages after a spinal cord crush did not affect the initial retraction of injured axons, but prevented later retraction that normally occurs after macrophages invade the spinal cord. In vitro studies on dorsal root ganglion neurons revealed that when an activated macrophage contacts a dystrophic axon, the macrophage adheres to and tugs on the axon, pulling it from the substrate and causing retraction. Together, these two studies suggest that whether myeloid cells help or hinder axon regeneration may depend on what type of myeloid cells are present (i.e., what subtypes of macrophages and granulocytes) and where and how macrophages are activated (e.g., by peripheral or CNS cues). Many macrophages (green) but few astrocytes (blue) were present at a lesion site 7 d after nerve crush (left). Treatment with toxic liposomes greatly reduced the number of macrophages, but astrocytes remained.

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