Macrophages migration through the brain parenchyma to the perivascular space following particle ingestion

Abstract

Forty-eight rats received intracerebral injections of sterile colloidal carbon. At intervals between 10 minutes and 31 days after carbon injection, the rats were perfused with glutaraldehyde, and autopsies were performed. Between 10 minutes and 3 hours after injection, carbon particles were extracellular and located strictly within the needle track. During the first few days the carbon was ingested by macrophages. Initially absent, carbon-laden macrophages spread to the neuropil immediately surrounding the injection site at 7 to 31 days following injection. These carbon-laden macrophages frequently were elongated within the neuropil and resembled microglia. Carbon-laden macrophages eventually accumulated around local vessels and in perivascular spaces. Many macrophages containing carbon remained in the injection site at the longest sampling interval of 31 days. Results indicate two macrophage responses to colloidal carbon in the central nervous system: a) an indolent population remains in the injection site for at least 1 month and b) a second population of macrophages emigrates through the neuropil. They eventually surround local vessels and enter the perivascular space. The migrating macrophages offer an explanation for the peculiar perivascular cells in Krabbe's disease and may provide a link between the CNS parenchyma and immunocompetent cells.