CD163/Hemoglobin Oxygenase-1 Pathway Regulates Inflammation in Hematoma Surrounding Tissues after Intracerebral Hemorrhage

Background: The aim of the present study was to investigate changes in the expression of CD163 and hemoglobin oxygenase-1 (HO-1) in brain tissue surrounding hematomas after intracerebral hemorrhage (ICH), and correlations with other factors. Materials and methods: Brain tissues in the close surrounding of ICH hematomas (n = 27, ICH group) were collected at 6 hours or less, 6-24 hours, 24-72 hours, and more than 72 hours after bleeding onset, and more distant tissues (n = 12, control group) were histologically analyzed with hematoxylin and eosin staining and transmission electron microscopy. Interleukin (IL)-1, IL-10, and tumor necrosis factor-alpha, as well as the expression of CD163 and HO-1, were assessed using immunochemistry, Western blotting, and reverse transcription-polymerase chain reaction. Apoptosis rates were determined with terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Results: The expressions of the inflammatory cytokines IL-1 and tumor necrosis factor-alpha were increased at 6-24 hours (P < .05), reached a peak at 24-72 hours (P < .001 and P < .01), at which time histopathological changes became most obvious and apoptosis rates were highest, but diminished for more than 72 hours after ICH onset. The anti-inflammatory cytokine IL-10 peaked at 6-24 hours (P < .01) after ICH onset but dropped in the following periods to lower levels than the control (P <.05). CD163 and HO-1 expressions gradually increased from 6 to 24 hours to peaks at more than 72 hours after ICH onset (P < .001). Conclusion: The highest inflammation level in tissues surrounding ICH hematomas occurred 2-3 days after bleeding onset, but was accompanied by an anti-inflammatory factor IL-10 expression enhancement. In the period of more than 72 hours after ICH onset, CD163 and HO-1 expressions reached peaks and inflammatory cytokine expressions dropped.