Abstract TMP114: Characterizing Anemia’s Impact on Cerebral Immune Response after Intracerebral Hemorrhage

Background: Anemia is a risk factor for worse intracerebral hemorrhage (ICH) outcomes, yet the underlying drivers remain unclear. Though anemia and inflammation are interrelated, it is unknown whether anemia influences inflammatory responses to ICH. We investigated the impact of anemia on inflammatory cell phenotypes seen in murine brains with and without ICH. Methods: Two different models of anemia were generated from 8-week-old, female C57/BL6 mice. The separate cohorts included: 1) chronic anemia model via iron-deficient chow compared to iron replete control diet, and 2) acute anemia model via red blood cell hemolysis using anti-TER119 injection compared to IgG control injection. After confirmation of anemia vs control via modified Drabkin assays, ICH was induced via collagenase injection into the right striatum, and brains and peripheral blood harvested 24 hours after ICH. Separate single cell suspensions were prepared from ICH and non-ICH hemispheres as well as peripheral blood and cells were stained for immunophenotyping using flow cytometry. Similar procedures were performed in mice without ICH. Two-tailed Student's t-tests were performed to compare immune cell populations between anemic vs non-anemic mice. Results: We identified a robust cerebral immune response to ICH in all groups. In the chronic anemia model, infiltrating macrophages and lymphocytes, particularly T cells, were elevated, while helper and gamma-delta T cells were lower in the ICH hemisphere in iron deficient anemic mice compared to iron replete controls (p<0.05). However, in the acute anemia model, only non-parenchymal intracranial macrophages were significantly elevated in the ICH hemisphere in anemic anti-TER119 injected mice compared to IgG injected controls (p<0.05). Notably, we observed a significant increase in infiltrating lymphocytes in the contralateral hemispheres in both acute and chronic models of anemia, compared to non-anemic controls. These findings in the brain were distinct from peripheral blood, where no major differences in immune cell populations were noted. Finally, in anemic mice without ICH, we did not identify a differential cerebral immune response compared to non-anemic controls. Conclusions: Anemia can differentially impact the inflammatory response to ICH in the central nervous system, based on its etiology and chronicity. Further work is required to assess whether anemia modification can abrogate pathologic immune pathways and improve ICH outcomes.