Haptoglobin and Hemopexin Redirect Heme-Driven Oxidative Stress and Neurotoxicity in Organotypic Brain Slices.

ABSTRACT: Hemorrhagic stroke triggers secondary brain injury through the red blood cell toxins hemoglobin (Hb) and heme, which fuel iron-driven lipid peroxidation and neuronal injury. We sought to use organotypic brain-slice cultures to dissect how the high-affinity scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) modulate this cascade. By day 7 of culture, slices remained structurally intact, metabolically active, and responsive to oxidative stress, enabling precise toxin exposure studies. Isotopic ⁵⁸Fe tracing revealed that upon cell-free Hb and heme exposures, heme-iron accumulated in brain slices and heightened lipid peroxidation. In contrast, Hpx neutralized heme, nearly abolishing iron deposition, while Hp partially reduced Hb-driven iron accumulation. Both scavengers attenua

SUBMITTER: Stalder AT 

PROVIDER: S-EPMC12784396 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature