Specific And Local Overexpression Of Hemopexin Improves Anatomical And Functional Outcomes In The Autologous Blood Intracerebral Hemorrhage Model

Intracerebral hemorrhage (ICH) has the highest morbidity, disability, and mortality rates of any stroke subtype, including ischemic stroke. When a hemorrhagic stroke occurs, the blood-brain barrier is broken and blood components enter the brain. A major cause of morbidity and mortality following ICH is the direct toxicity of blood metabolites, notably free heme, on adjacent brain tissue. Hemopexin (Hpx) is the endogenous protein responsible for scavenging free heme; thereby, modulating its proxidant and proinflammatory properties. Given the low relative level of Hpx expression in the brain, we hypothesized that overexpression of Hpx would improve anatomical and functional outcomes after ICH. Unique adeno-associated viral vectors (and control vectors) were designed to specifically overexpress Hpx-(tags) locally within the brain. Hpx-overexpressing mice have smaller lesion volumes (pu003c0.05) and reduced blood accumulation (pu003c0.05) at 72h post-ICH (n=12-13/group). Improved anatomical outcomes are also associat...