Hemoglobin (Hb) released by RBC lysis following ICH causes neuroinflammation and cell death, inflicting irreversible brain damage. Haptoglobin (Hp) and CD163 form a scavenging system for Hb to protect tissues from its cytotoxic effects: Hp binds to Hb, and this complex is endocytosed by macrophages-microglia expressing the CD163 receptor. There is no effective treatment against ICH, and limited research exists on the respective functions of Hp and CD163 after ICH. We investigated the effects that Hp and CD163 have on outcomes after ICH in knockout animals.
   ICH was induced by collagenase in WT control, CD163-/-, Hp-/-, and Hp-/-xCD163-/- mice. Functional and anatomical outcomes were assessed at 24, 48 and 72h following ICH. Lesion volume and hematoma volume in CD163-/- mice was 27.5+/-5.8% and 30.6+/-4.6% smaller compared to WT. Lesion volume in Hp-/- mice was 28.2+/-7.2% smaller compared to WT. No significant differences were detected between Hp-/-xCD163-/- and WT mice. Additional data are as follow: Hp-/- mice had smaller hemispheric enlargement and BBB breakdown compared to WT mice, less iron and astrogliosis compared to WT and CD163-/- mice, and less induction of heme oxygenase compared to all other groups. The CD163-/- mice had less total Hb in brain tissue and less blood-brain barrier breakdown compared to WT mice. The Hp-/-xCD163-/- mice had less blood-brain barrier breakdown compared to WT mice.
   These initial findings demonstrate the differences in recovery following ICH. The outcomes of this preclinical study help in the design of future clinical trials to limit devastating brain damage following ICH.

Role of the Haptoglobin-CD163 Scavenging System in Intracerebral Hemorrhage