Characterizing Border Associated Macrophages during spinal cord regeneration

The human central nervous system has limited regenerative ability, with injuries to the spinal cord (SC) often resulting in paralysis. Alternatively, zebrafish have enhanced innate regenerative capacity and regain full motor function following spinal cord injury (SCI). Immune activation following SCI is necessary to provide a permissive environment for tissue repair, but the immune pathways necessary for SC regeneration are not well characterized. In previous data, we have found that while immune activation is persistent into the chronic phases of SCI response in mammals, zebrafish achieve full immune clearance within 48 days post SCI. We hypothesize that one key distinction driving these differences between the mammalian and zebrafish SCI immune response is an accelerated repair of the blood SC barrier following SCI. In the current study, we investigated post-injury gene expression and function of a specific immune subpopulation, Border Associated Macrophages (BAMs). BAMs are specialized immune cells positioned at the junction of the central nervous system and the peripheral blood. Through gene ontology analysis and a single nuclear RNA-sequencing atlas of the regenerating SC, we have identified putative BAM markers. In future studies, we aim to ablate BAMs and test blood SC barrier reformation and SC regeneration. Together, these studies will identify pro-regenerative immune pathways that can be used as therapeutic targets for human SCI patients.