Spatiotemporal pattern of macrophage recruitment after chronic nerve compression injury.

The contribution of macrophages to the pathogenesis of chronic nerve compression (CNC) injuries is presently unclear. We examined the time course and spatial localization of macrophage invasion from 24 hours to 28 days post-CNC injury with immunohistochemistry (IHC) and electron microscopy (EM). To clarify the differences in macrophage activity between different peripheral nerve injuries, we compared CNC injury to a nerve crush (CR) injury at similar time points. Entire counts of macrophages with ED1-immunoreactivity (IR) showed a slow, gradual increase in macrophage number from 24 hours to 28 days post-operatively in compressed sections. ED1-IR was greatest at the site of compression and in distal nerve segments with minimal immunostaining in proximal and normal sections. Quantitative analysis of ED1-IR after crush injury demonstrated a rapid time course of macrophage recruitment with ED1-IR peaking at 48 hours and declining to normal values as early as 21 days post-CR injury. Ultrastructural analysis with EM 14 days post-CNC injury revealed greater macrophage localization in the inner one-third region of normal nerves relative to the outer region. Differences in macrophage localization within inner and outer regions of compressed sections were negligible, as macrophages were found diffusely throughout the endoneurium by day 14. Our findings suggest that macrophage recruitment is dependent upon proximity to neural vasculature with relative macrophage density highest specifically around endoneurial blood vessels in both normal and compressed sections. Taken together, our results detail the unique spatiotemporal dynamics of macrophage recruitment early after CNC injury as distinct from a crush injury.