Dynamic microglia/macrophage infiltration during spinal cord regeneration in larval sea lamprey.

Abstract

Both mammals and non-mammalian vertebrates display neuroimmune interactions after spinal cord injury (SCI). However, the impact of the immune response on neural regeneration remains unclear as it includes both proregenerative and inhibitory processes. To begin to understand how neuroimmune interactions influence central nervous system (CNS) regeneration, we examined the distribution of microglia/macrophages in relation to regenerating axons in larval sea lamprey (Petromyzon marinus), a non-mammalian vertebrate that exhibits robust axon and synapse regeneration after SCI. The relationship between microglia/macrophages and spinal axons was examined in cryosections of control and transected spinal cords using immunofluorescence. SCI significantly increased microglia/macrophage density within the spinal cord, as shown by isolectin B4 labeling. At 11 weeks post-injury (WPI), microglia/macrophages made physical contacts with regenerating axons, on average a three-fold increase compared to controls. These results are consistent with the conclusion that microglia/macrophage infiltration is associated with axon regeneration. Understanding the importance of these neuroimmune interactions could bring insight into cellular and molecular mechanisms that promote regeneration in the mammalian CNS.