Hematoma Changes During Clot Resolution After Experimental Intracerebral Hemorrhage

Abstract

Background and Purpose Hematoma clearance occurs in the days after intracerebral hemorrhage (ICH) and has not been well studied. In the current study, we examined changes in the hematoma in a piglet ICH model. The effect of deferoxamine on hematoma was also examined. Methods The ICH model was induced by an injection of autologous blood into the right frontal lobe of piglets. First, a natural time course of hematoma changes up to 7 days was determined. Second, the effect of deferoxamine on hematoma changes was examined. Hemoglobin and membrane attack complex levels in the hematoma were examined by enzyme-linked immunosorbent assay. Immunohistochemistry and Western blotting was used to examine CD47 (a regulator of erythrophagocytosis), CD163 (a hemoglobin scavenger receptor) and heme oxygenase-1 (a heme degradation enzyme) in the clot. Results After ICH, there was a reduction in red blood cell diameter within the clot with time. This was accompanied by membrane attack complex accumulation and decreased hemoglobin levels. Erythrophagocytosis occurred in the hematoma and this was associated with reduced clot CD47 levels. Activated macrophages/microglia were CD163 and hemeoxygenase-1 positive and these accumulated in the clot with time. Deferoxamine treatment attenuated the process of hematoma resolution by reducing member attack complex formation and inhibiting CD47 loss in the clot. Conclusion These results indicate that membrane attack complex and erythrophagocytosis contribute to hematoma clearance after ICH, which can be altered by deferoxamine treatment.

Rehabilitation Augments Hematoma Clearance and Attenuates Oxidative Injury and Ion Dyshomeostasis After Brain Hemorrhage

“…For example, CD47 inhibits erythrocyte phagocytosis and limits hematoma clearance. 23 By contrast, accumulation of CD163 + and HO-1 + microglia/macrophages and membrane attack complexes are associated with improved hemoglobin clearance. 23 In addition, the Nrf2 pathway mediates erythrocyte phagocytosis and increases antioxidant production.…”

Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage

“…CD163 is mainly expressed on macrophages/microglia and it plays a major role in scavenging free hemoglobin released during erythrolysis (11, 12). In ICH patients, the expression of CD163 increased around the hematoma (13) and our recent study found that CD163 positive cells are present and are significantly increased in the hematoma in the first 24 hours in a pig ICH model(14). …”

CD163, a Hemoglobin/Haptoglobin Scavenger Receptor, After Intracerebral Hemorrhage: Functions in Microglia/Macrophages Versus Neurons

“…As such, CD163 expression is significantly increased in the hematoma within 24 h [14]. This is most likely due to a combination of migration of M2 microglia into the hematoma, infiltration of new M2 macrophages from the circulation, and gene upregulation in microglia/macrophages.…”

“…CD163 expression in hematoma and perihematomal increases with time after ICH [14,17,18]. In humans, Liu et al [17] found a progressive increase in the number of perihematomal CD163-positive cells between 6 and 72 h after ICH.…”

“…Thus, following ICH, there is a gradual loss of hemoglobin from the hematoma [14]. The brain may be particularly susceptible to hemoglobin-induced injury because normal brain levels of the hemoglobin scavenger haptoglobin are very low; the CSF haptoglobin concentration is~800 μg/L in humans, compared to 1.4 g/L in serum [15].…”