Abstract W P237: Overexpression of Soluble Hemopexin as a Therapeutic Tool against Intracerebral Hemorrhage
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, mainly free heme, on adjacent brain tissue. Hemopexin (Hpx) is the endogenous protein responsible for scavenging free heme; thereby, modulating its proxidant and proinflammatory properties. We hypothesized that the specific local overexpression of Hpx within the brain would attenuate anatomical and functional outcomes after experimentally inducing an ICH. We uniquely designed novel adeno-associated viral vectors (and control vectors) to specifically overexpress Hpx locally within the brain of C57BL/6N mice. After experimentally inducing an ICH using the autologous whole blood model, when compared to an identically treated control group, Hpx-overexpressing mice were found to have reduced brain injury volume at 72h post-ICH (p<0.05), as identified by lesion volume quantification of Cresyl Violet stained brain sections (n=7-9/group). Further, these anatomical outcomes were correlated with improved neurologic recovery, as measured by a 24-point neurological deficit scale, at 24h, 48h, and 72h post-ICH (p<0.05). Modulation of hemopexin levels would represent a clinically relevant strategy for the treatment of secondary brain injury following ICH. Further studies are needed in order to evaluate the in vivo utility of hemopexin in attenuating oxidative damage following hemorrhagic brain injury.
Author Disclosures: J.L. Leclerc: None. A. Dang: None. J. Santiago-Moreno: None. S. Doré: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate – Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico, Tennessee, U.S. Virgin Islands.
- © 2015 by American Heart Association, Inc.