Research ReportBone-marrow mononuclear cells reduce neurodegeneration in hippocampal CA1 layer after transient global ischemia in rats

- BMMC injection reduced neurodegeneration in the CA1 layer of the hippocampus.
- BMMC therapy reduced reactive microgliosis in the CA1 layer of ischemic animals.
- Homing of 99mTc-BMMCs in the brain was low, yet higher in ischemic animals.

Global cerebral ischemia (GCI) results in death of the pyramidal neurons in the CA1 layer of the hippocampus. In this study we used the four-vessel occlusion (4VO) model of GCI to investigate a potential neuroprotective role of bone-marrow mononuclear cells (BMMCs) transplantation. BMMCs (3×107) were injected through the carotid artery, 1 or 3 days after ischemia (DAI), and the number of cells undergoing degeneration was investigated in brains at 7 DAI. A significant decrease in the number of dying cells was observed in the treated group, compared to animals treated with saline. Biodistribution of the injected cells (1 or 3 DAI) was investigated by 99mTechnetium labeling of the BMMCs and subsequent image analysis 2 h after transplantation. In addition, the presence of CellTrace™-labeled BMMCs was investigated in tissue sections of the hippocampal area of these transplanted animals. BMMCs treatment significantly reduced the number of FJ-C positive cells in the hippocampal CA1 layer at 7 DAI. We also observed a decrease in the number of activated microglia/macrophage (ED1-positive cells) in the BMMCs-treated group compared with the untreated group. Our data show that BMMCs are able to modulate the microglial response and reduce neurodegeneration in the CA1 layer.