Transient ischemia-induced paresis and complete paraplegia displayed distinct reactions of microglia and macrophages

In this study, we perform a detailed analysis of the microglial and macrophage responses in a model of spinal cord ischemia and reperfusion (SCI/R) injury in Wistar rats. The rats underwent occlusion across the descending aorta for 13min, causing paraplegia or paresis of varying severity. They were divided into four groups based on neurological assessment: sham, mild paresis, moderate paresis, and severe (complete) paraplegia. To examine the origin of microglia and macrophages in the ischemic lesion, bone marrow from rats expressing green fluorescent protein (GFP) was transplanted into test subjects one month before performing SCI/R. Many GFP(+)/CD68(+) microglia and macrophages were present 7d after SCI/R. Resident (GFP(-)/Iba1(+)/CD68(-)) microglia and bone marrow-derived macrophages (BMDMs; GFP(+)/Iba1(+)/CD68(+)) colocalized in the mild group 7d after SCI/R. In the moderate group, BMDMs outnumbered resident microglia. A greater accumulation of BMDMs expressing insulin-like growth factor-1 (IGF-1) was observed in lesions in the severe group, relative to the moderate group. BMDMs in the severe group strongly expressed tumor necrosis factor α, interleukin-1β, and inducible nitric oxide synthase, in addition to IGF-1. A robust accumulation of BMDMs occupying the entire ischemic gray matter was observed only in the severe group. These results demonstrate that the magnitude of the microglial and BMDM responses varies considerably, and that it correlates with the severity of the neurological dysfunction. Remarkably, BMDMs appear to have a beneficial effect on the spinal cord in paresis. In contrast, BMDMs seem to exhibit both beneficial and harmful effects in severe paraplegia.