Heme toxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The primary defense against extracellular heme is provided by hemopexin, a serum and neuronal glycoprotein that binds it with very high affinity and mitigates its prooxidant effect. In the present study, the authors tested the hypothesis that hemopexin knockout mice would sustain more injury after experimental ICH than their wild-type counterparts.
Striatal ICH was induced by the stereotactic injection of bacterial collagenase or autologous blood. Three days later, striatal protein oxidation was assessed via carbonyl assay. Cell viability was quantified at 8–9 days by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Behavioral deficits were detected with high-resolution digital analysis of 6-hour home cage video recordings and standard testing.
Perihematomal protein oxidation was increased in wild-type collagenase-injected striata by approximately 2.1-fold, as compared with contralateral striata; protein carbonyls were increased 3-fold in knockout mice. Striatal cell viability was reduced by collagenase injection in wild-type mice to 52.9 ± 6.5% of that in the contralateral striata, and to 31.1 ± 3.7% of that in the contralateral striata in knockout mice; similar results were obtained after blood injection. Digital analysis of 6-hour video recordings demonstrated an activity deficit in both models that was significantly exacerbated at 8 days in knockout mice. Striatal heme content 9 days after blood injection was increased approximately 2.7-fold in knockouts as compared with wild-type mice.
These results suggest that hemopexin has a protective effect against hemorrhagic CNS injuries. Hemopexin deficiency, which is often associated with sickle cell disease, may worsen outcome after ICH.
Abbreviations used in this paper: ICH = intracerebral hemorrhage; MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PCR = polymerase chain reaction; TTC = 2,3,5-triphenyltetrazolium chloride.
Address correspondence to: Raymond F. Regan, M.D., Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut Street, College Building Room 813, Philadelphia, Pennsylvania 19107. email: Raymond.Regan@jefferson.edu.
Please include this information when citing this paper: published online December 3, 2010; DOI: 10.3171/2010.10.JNS10861.
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