Turnover of rat brain perivascular cells

Brain perivascular spaces harbor a population of cells which exhibit high p hagocytic capacity. Therefore, these cells can be labeled by intraventricul ar injection of tracers. Such perivascular cells at the interface between b lood and brain are believed to belong to the monocyte/macrophage lineage an d to be involved in antigen presentation. Currently, it is unclear whether these cells undergo a continuous turnover by entering and leaving the blood stream. Using bone-marrow-chimeric animals, migration of donor macrophages into brain perivascular spaces has been reported. On the other hand, follow ing intracerebral injection of india ink into nontransplanted animals, ink- labeled perivascular cells were still found 2 years after injection, sugges ting a high stability of this cell pool. Thus, the turnover of perivascular cells observed in chimeras might be a result of bone marrow transplantatio n rather than a physiological occurrence. To address this issue, we monitor ed de novo invasion of macrophages into perivascular spaces of apparently h ealthy adult rats by applying techniques other than bone marrow transplanta tion, (i) consecutive injections of different tracers and (ii) ex vivo isol ation of macrophages from the blood, cell labeling, and reinjection into th e same animal to avoid MHC mismatch. Both approaches revealed vivid de novo invasion of macrophages into perivascular spaces, but not into brain paren chyma, rendering untenable the concept of perivascular cells forming a stab le population of macrophages in the brain. Thus, brain perivascular spaces are under permanent immune surveillance of blood borne macrophages in norma l adult rats. (C) 2001 Academic Press.