Immune cell response after intracerebral hemorrhage in piglets and the treatment effects of deferoxamine and minocycline

Qing Xie; Yuxiang Gu; Guohua Xi; Ya Hua; Richard F Keep; Yingfeng Wan

doi:10.1016/j.expneurol.2025.115354

Immune cell response after intracerebral hemorrhage in piglets and the treatment effects of deferoxamine and minocycline

Exp Neurol. 2025 Jun 23:115354. doi: 10.1016/j.expneurol.2025.115354. Online ahead of print.

Authors

Qing Xie¹, Yuxiang Gu¹, Guohua Xi¹, Ya Hua¹, Richard F Keep¹, Yingfeng Wan¹

Affiliation

¹ Departments of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.

PMID: 40562342
DOI: 10.1016/j.expneurol.2025.115354

Abstract

Background: Intracerebral hemorrhage (ICH) induces immune cell infiltration. This study used a piglet lobar ICH model to address three questions: do immune cells use surviving or degenerating white matter within hematoma to migrate? Do certain types of immune cell preferentially migrate into the hematoma? How do two potential therapeutics, deferoxamine (DFX) and minocycline (MINO), alter the migration of different immune cells into the perihematomal zone and the hematoma itself?

Methods: This two-part study was conducted in piglets. In the first part, 2.5 ml of blood was injected into the right frontal lobe, and the animals were euthanized at 4 h, days 1, 3 and 7 post-ICH. In the second part, animals were treated with vehicle, DFX or MINO after ICH and euthanized on day 3. Immunohistochemistry was used to examine the distribution of B and T lymphocytes, neutrophils and microglia/macrophages in the hematoma and perihematomal areas.

Results: B and T lymphocytes, as well as microglia/macrophages, gradually increased in the hematoma and peri-hematomal areas from 4 h to day 7 after ICH, while neutrophils decreased from 4 h to day 1 before increasing from day 1 to day 7. The infiltration of all the types of immune cells into the hematoma core was greater in areas with surviving intra-hematoma white matter fibers. There was preferential migration of B and T lymphocytes compared to microglia/macrophages as assessed by the hematoma/perihematomal ratio. MINO treatment significantly reduced infiltration of B and T lymphocytes and microglia/macrophages into the hematoma and peri-hematomal area at day 3 post-ICH. DFX induced a non-significant reduction. However, neutrophil numbers increased in the hematoma and peri-hematomal areas with DFX, while MINO reduced neutrophil numbers.

Conclusions: ICH induces significant infiltration of immune cells infiltration into the hematoma core and perihematomal areas, with this infiltration associated with surviving intra-hematoma white matter fibers. DFX and MINO treatments attenuate the immune cells response, although DFX increase neutrophils number, possible due to reduced neutrophils apoptosis.

Keywords: Deferoxamine; Intracerebral hemorrhage; Lymphocyte; Macrophages; Microglia; Minocycline; Neutrophil; Piglet.