Shenglong Cao1, Mingzhe Zheng1, Ya Hua1, Gao Chen1, Richard F Keep1, Guohua Xi2. 1. From the Department of Neurosurgery, University of Michigan, Ann Arbor (S.C., M.Z., Y.H., R.F.K., G.X.); and Department of Neurosurgery, the 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China (S.C., G.C.). 2. From the Department of Neurosurgery, University of Michigan, Ann Arbor (S.C., M.Z., Y.H., R.F.K., G.X.); and Department of Neurosurgery, the 2nd Affiliated Hospital, Zhejiang University, Hangzhou, China (S.C., G.C.). guohuaxi@umich.edu.
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 ≤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 were 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. CONCLUSIONS: These results indicate that membrane attack complex and erythrophagocytosis contribute to hematoma clearance after ICH, which can be altered by deferoxamine treatment.
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 ≤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 were 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. CONCLUSIONS: These results indicate that membrane attack complex and erythrophagocytosis contribute to hematoma clearance after ICH, which can be altered by deferoxamine treatment.
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