Neuroprotective effect of heme oxygenase-2 knockout in the blood injection model of intracerebral hemorrhage

被引:17
作者
Chen-Roetling J. [1 ]
Cai Y. [1 ]
Regan R.F. [1 ]
机构
[1] Department of Emergency Medicine, Thomas Jefferson University, College Building, 1025 Walnut Street, Philadelphia, 19107, PA
基金
美国国家卫生研究院;
关键词
Neurological Outcome; Blood Injection; Collagenase Injection; Contralateral Striata; Corner Test;
D O I
10.1186/1756-0500-7-561
中图分类号
学科分类号
摘要
Background: The toxicity of heme breakdown products may contribute to the pathogenesis of intracerebral hemorrhage (ICH). Heme catabolism is catalyzed by the heme oxygenase enzymes. We have previously reported that heme oxygenase-2 (HO-2), the constitutive isoform, protects neurons from hemin in vitro and reduces oxidative stress after striatal blood injection. In order to further evaluate HO-2 as a therapeutic target, we tested the hypothesis that HO-2 gene deletion protects neurons and attenuates behavioral deficits after ICH. Findings. Injection of 20 μl blood into the right striatum of HO-2 wild-type mice resulted in loss of approximately one third of striatal neurons 4-8 days later. Neuronal survival was significantly increased in HO-2 knockout mice at both time points. This was associated with reduced motor deficit as detected by the corner test; however, no differences were detected in spontaneous activity or the adhesive removal or elevated body swing tests. Conclusion: HO-2 knockout attenuates perihematomal neuron loss in the blood injection ICH model, but has a weak and variable effect on neurological outcome. © 2014 Chen-Roetling et al.; licensee BioMed Central Ltd.
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