5. Intra bone marrow procedure facilitates entry of transplanted bone marrow cells through the tenia of choroid plexus into brain parenchyma

Abstract

Although the immune system modulates the brain function under steady-state conditions, it has not been clear where and how the peripheral immune cells interact with brain parenchymal cells. We created radiation chimera mice in which recipients’ immune system was reconstituted by bone marrow cells derived from donor GFP transgenic mice by a novel intra-bone marrow–bone marrow transplantation (IBM–BMT) method and by conventional intravenous (IV)–BMT. We examined the distribution, differentiation and density of donor-derived bone marrow (BM) cells in the brain parenchyma 2 weeks and 1, 4 and 8 months after the BMT. We found BM-derived cells in several discrete brain regions mostly adjacent to the tenia of the choroid plexus from 1 to 4 months after BMT, but not in the remaining major parts until 8 months after BMT. BM-derived cells exhibited ramified morphology and expressed Iba-1 but not GFAP, CNPase or NeuN, indicative of the myeloid lineage. The densities of BM-derived cells in the brain parenchyma increased in a time dependent manner after IBM–BMT but not after IV–BMT, therefore the BM-derived cell densities 8 months after IBM–BMT were significantly higher than those after IV–BMT. The choroid plexus stroma contained more BM-derived cells after IBM–BMT than after IV–BMT. These results suggested that the tenia of the choroid plexus represents a novel route of entry for peripheral immune cells into the brain parenchyma under steady-state conditions.