Lesional accumulation of CD163+ macrophages/microglia in rat traumatic brain injury.

A robust neuroinflammation, contributing to the development of secondary injury, is a common histopathological feature of traumatic brain injury (TBI). Characterization of leukocytic subpopulations contributing to the early infiltration of the damaged tissue might aid in further understanding of lesion development. Reactive macrophages/microglia can exert protective or damaging effects in TBI. CD163 is considered a marker of M2 (alternatively activated) macrophages. Therefore we investigated the accumulation of CD163(+) macrophages/microglia in the brain of TBI rats. TBI was induced in rats using an open skull weight-drop contusion model and the accumulation of CD163(+) cells was analyzed by immunohistochemistry. In normal rat brains, CD163 was expressed by meningeal, choroid plexus and perivascular macrophages. Significant parenchymal CD163(+) cell accumulation was observed two days post TBI and continuously increased in the investigated survival time. The accumulated CD163(+) cells were mainly distributed to the lesional areas and exhibited macrophage phenotypes with amoeboid morphologic characteristics but not activated microglial phenotypes with hypertrophic morphology and thick processes. Double-labeling experiments showed that most CD163(+) cells co-expressed heme oxygenase-1 (HO-1). In addition, in vitro incubating of macrophage RAW264.7 cells or primary peritoneal macrophages with hemoglobin- haptoglobin (Hb-Hp) complex suppressed LPS-induced inflammatory macrophages phenotype and induced CD163 and HO-1 upregulation, indicating that CD163(+) macrophages/microglia in TBI might have anti-inflammatory effects. And further study is necessary to identify functions of these cells in TBI.