Temporal changes in monocyte and macrophage subsets and microglial macrophages following spinal cord injury in the lys-egfp-ki mouse model

•The microglial response dominates over the myeloid response in the spinal lesion•In SCI lesions classical macrophage dominate acutely, decline then return chronically•Non-classical macrophages arise subacutely and persist chronically in spinal lesions

The role of hematogenous (hMΦ) and microglial (mMΦ) macrophages following spinal cord injury (SCI) remains unclear as they are not distinguished easily from each other in the lesion area. We have recently described the temporal and spatial response to SCI of each MΦ population using the lys-EGFP-ki mouse that enables EGFP+ hMΦ to be distinguished from EGFP− mMΦ at the lesion site. In the present study, we characterized the response of monocyte and hMΦ subsets and mMΦ to SCI. We describe, for the first time, the responses of circulating classical (pro-inflammatory) and non-classical monocyte subsets to SCI. Additionally, we show the presence of classical and non-classical hMΦ at the SCI lesion. Importantly, we demonstrate that the 'classical pro-inflammatory' hMΦ respond in the acute (1 d, 3 d) stages of SCI while the 'non-classical' hMΦ respond in the sub-acute (7 d, 14 d) phase of SCI. At later time points (6 weeks post injury) classical hMΦ return to the injury site. Our study offers new insight into the cellular inflammatory response that occurs after SCI and suggests that the timing and targets of anti-inflammatory therapies may be crucial to maximize neuroprotection at the acute and more chronic stages of SCI.