Sciatic nerve conditioning lesion increases macrophage response but it does not promote the regeneration of injured optic nerves

Injured optic nerves in the matured central nervous system (CNS), alike injured neurons in other CNS regions, fail to regenerate. Interestingly, activation of inflammatory cells (macrophages) following optic lens injury or implantation of peripheral nerve fragments into the vitreous body, have been previously reported to stimulate retinal ganglion cells (RGCs) to regenerate axons across the injury site and into the distal optic nerve. In addition, the beneficial role of macrophage cells has also been demonstrated in the regeneration of lesioned spinal neurons following sciatic nerve injury. However, it is not known whether these locally activated macrophage cells also contribute to the regeneration of remotely injured neurons within the CNS. Adult Sprague Dawley rats received a conditioning sciatic nerve injury followed by an optic nerve crush (ONC). Retrograde and anterograde tracing results revealed that injured optic axons did not regenerate after peripheral dorsal root ganglion (DRG) lesion, as the beneficial effects of this injury extended only locally. However, a greater inflammatory infiltration/activation was found in injury-combined animals compared to controls, although this was not sufficient to trigger a systemic regenerative response. Proximity of cell body response to injury, accompanied by a timely macrophage activation are critical factors for regeneration of injured CNS neurons to occur. Immune cell surveillance into the CNS compartment was enhanced following peripheral nerve injury.Scope: nervous system development, regeneration and aging.

Research Highlights
► Sciatic nerve lesion does not stimulate axonal regeneration of injured optic nerves.
► Proximity of cell body response to injured axons is crucial for CNS regeneration.
► Sciatic nerve lesion promotes macrophage infiltration into the CNS compartment.
► Macrophage migratory pattern in CNS regions differs after sciatic nerve lesion.