Increased brain hemopexin levels improve outcomes after intracerebral hemorrhage

Following intracerebral hemorrhage (ICH), extracellular heme precipitates secondary brain injury, which results in irreversible brain damage and enduring neurological deficits. Hemopexin (Hpx) is an endogenous protein responsible for scavenging heme, thereby modulating its intrinsic proxidant/proinflammatory properties. Although Hpx is present in the brain, the endogenous levels are insufficient to combat the massive heme overload following ICH. We hypothesized that increasing brain Hpx levels would improve ICH outcomes. Unique recombinant adeno-associated viral vectors were designed to specifically overexpress Hpx within the mouse brain. Western blotting, ELISA, and immunohistochemistry of brain homogenates/sections, CSF, and serum were performed. As compared to controls, Hpx mice have increased Hpx protein levels in all three types of biospecimens evaluated, which results in 45.6 ± 6.9% smaller lesions and improved functional recovery after ICH (n=14–19/group, p < 0.05). Local mechanistic analyses show ...