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.

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To improve the possibilities of delimitating the time of death after longer laytime it was examined if this is possible by immunohistochemical glucagon detection. The results show that in our examination material the pancreatic alpha-cells of up to 6-day-old corpses produce a positive immunoreaction towards glucagon in all cases whereas none of the corpses older than 14 days show such a reaction. This means that in the case of a negative immunoreaction the time of death can be assumed to lie more than 7 days before the autopsy. The fact that a negative immunoreaction occurs consistently after 14 days leads to the conclusion that when glucagon has been stained in a specimen, the death of the respective person must lie a maximum of 13 days earlier, whereby under markedly different conditions to the ones of the cases here examined, a negative immunoreaction could happen earlier and a positive immunoreaction even later.