Progression of axon degeneration (left panels) and macrophage accumulation (right panels) in mouse distal nerves after tight sciatic nerve ligation. Sciatic nerves from 129P3/J mice were harvested at the indicated timepoints post-injury. After sectioning nerves longitudinally, we used immunohistochemistry to visualize axons (PGP9.5) and macrophages (F4/80). Axons degenerate progressively, with early discontinuities visible within 1 day of injury, extensive degeneration at 3 days, and nearly complete degeneration within 7 days (axon regeneration is precluded by tight ligation of the sciatic nerve). Few macrophages reside within the uninjured (uninj.) nerve. Macrophage accumulation, which includes resident macrophage proliferation and hematogenous macrophage infiltration, begins by 1 day after injury and peaks between 3 and 7 days post-axotomy. Note the change in macrophage morphology and F4/80 immunoreactivity between 3 and 7 days: compact, elongated F4/80-positive cells predominate at 3 days, whereas most macrophages are large and amoeboid at 7 days post-axotomy. This switch reflects the phagocytosis of large amounts of debris by macrophages between those timepoints. Scale bar, 200 μm.