Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14

Abstract

Human traumatic brain injury (TBI) is ideally suited for investigation of the kinetics of human microglial cell activation as the onset of lesion formation is precisely defined. The present study provides evidence of a distinct delay in macrophage/microglia response following TBI. Eighteen brains of patients who had survived TBI for 1 h to 6 months were analysed by immunohistology. Samples of contusional and non-contusional areas were studied using antibodies directed against antigens of microglia/ macrophages [major histocompatibility complex class II, CD4, interleukin (IL)-16, macrophage-related protein (MRP) 8 and MRP14]. IL-16, a natural ligand to CD4, was expressed constitutively by numerous microglial cells in all cases throughout the brain. CD4 could be detected regularly on perivascular cells. MRP8 and MRP14, which are only expressed on activated macrophages and microglial cells, could be detected only within brains with a survival time of more than 72 h post TBI. In addition, proliferation of microglia detected by MIB-1 was not present until 72 h. This delayed expression of the activation markers MRP8 and MRP14 and the proliferation marker MIB-1 is comparable to experimental closed head injuries but strictly different from acute activation found in ischemic brains.

Traumatic Brain Injury and Inflammation: Emerging Role of Innate and Adaptive Immunity

“…Studies in humans with TBI have revealed a striking delay of microglial activation and proliferation. Markers of microglial activation and proliferation were not detected until 3 days post TBI (Beschorner et al, 2000;Engel et al, 2000) whereas the same markers were expressed early in cerebral ischemia (Postler et al, 1997). This observation although in line with some findings in experimental models (Aihara et al, 1995;Holmin et al, 1997) cannot be fully understood.…”

Physiology of Microglia

“…However, with lesion progression, the clear demarcation may fade, rendering an unequivocal identification more difficult. Other distinctions have been made by superoxide dismutase expression (250), whereas expression of the calcium binding macrophage related proteins MRP8/S100A8 and MRP-14/S100A9 is thought to identify circulating and more recently invaded monocytes/macrophages (375,490), while delayed expression in microglia can occur as well (249).…”

Memory-related gene expression profile of the male rat hippocampus induced by teeth extraction and occlusal support recovery

“…38 Cerebral ischemia, traumatic brain injury, and Alzheimer's disease (AD) have been reported to be associated with altered expression/function of S100 family members. 22,39,40,41 Recently, S100a9 was found to be increased within neuritic plaques and reactive glia, thus suggesting a role in the inflammatory component of AD pathogenesis. 22 Furthermore, inhibition of S100a9 may be a possible therapeutic target for AD.…”