THE CELLULAR REACTIONS TO EXPERIMENTAL INTRACEREBRAL HEMORRHAGE

The resolution of an intracerebral hemorrhage can be measured by the o ccurrence of hemosiderin. Extravasation of blood elicits a cellular re action in the adjacent surviving tissue where the lesion activates res ident microglia and attracts many more phagocytes from the blood strea m. The signals for this migration into the perifocal reactive zone are not fully understood but it is likely that proteins in the coagulated blood contribute to cellular activation, Tn order to study the role o f plasma proteins in the pathogenesis of the perifocal reactive zone, intracerebral injections of either autologous whole blood (0.1 ml) or an equal volume of washed autologous red blood cells (RBC) in lactated Ringer's solution were made in adult rabbits. The amount of total iro n was the same (30 mu g). The cellular responses to the injections wer e studied by iron histochemistry and immunocytochemistry for ferritin, the ferritin repressor protein (FRP), the glial fibrillary acidic pro tein (GFAP), and the complement receptor CR3. Experimental hematomas r esolved much more slowly after the injection of whole blood than after the injection of RBC. Qualitative microglial and astrocytic responses were quite similar. However, at 48 h, iron- and ferritin-reactive mic roglia were more numerous following the injection of whole blood. Afte r injections of either type, ferritin-immunoreactive cells were more a bundant than iron-positive cells. This observation implied that the bi osynthesis of holoferritin protein and iron incorporation proceeded in dependently. Expression of CR3 on the surface of microglia was much mo re prominent after whole blood, suggesting a role of inactivated compl ement 3b in the attraction of additional phagocytes. Conversion to hem osiderin began at 5 days after the injection of either blood or RBC. T he lesions caused initial destruction of astrocytes in the perifocal z one as judged by GFAP- and FRP-immunoreactivity. However, at 5 days, a strocytic processes reentered the perifocal zone and intermingled with microglia and macrophages. It is proposed that this contact between a strocytes and microglia reversed the uncoupling of ferritin biosynthes is and iron incorporation and initiated the storage of iron and format ion of hemosiderin.