Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord

Brain and spinal cord inflammation that develops after traumatic injury is believed to differentially influence the structural and/or physiological in tegrity of surviving neurons and glia. It is possible that the functional d ichotomy of CNS inflammation results from the activity of a heterogeneous m acrophage population elicited by trauma. Indeed. unique functions have been attributed to macrophages derived from resident microglia versus those ori ginating from infiltrating monocytes. Thus, whether progressive tissue inju ry or repair is favored could be explained by the disproportionate contribu tions of one macrophage subset relative to the other. Descriptive neuroanat omical studies are a reasonable first approach to revealing a relationship between microglia, recruited blood monocytes/macrophages, and regions of ti ssue degeneration and/or repair. Unfortunately, it is not possible to diffe rentiate between CNS macrophage subsets using conventional immunohistochemi cal approaches. In the present study, we have used radiation bone marrow ch imeric rats to definitively characterize the macrophage reaction elicited b y experimental spinal contusion injury. In chimeric animals, antibodies rai sed against unique cell surface molecules expressed on bone marrow-derived cells (BMCs) were used to distinguish infiltrating BMCs from resident micro glial-derived macrophages. Our findings indicate that the onset and plateau of macrophage activation (previously shown to be 3 and 7 days postinjury, respectively) is dominated initially by microglial-derived macrophages and then is supplanted by hematogenous cells. While resident macrophages are ub iquitously distributed throughout the injury site, leukocyte-derived monocy tes exclusively infiltrate the gray matter and ro a lesser extent subpial w hite matter. Generally, monocyte foci in white matter remain associated wit h the lumen or abluminal surface of blood vessels. i.e. few cells actually infiltrate the parenchyma. If functional differences exist between CNS macr ophage subsets, differences in the time-dependent accumulation and distribu tion of these cell types could differentially influence the survival of sur rounding neurons and glia.