Intracerebral Hemorrhage in Mice: Model Characterization and Application for Genetically Modified Mice

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Abstract
Gene knockout or transgenic animals may assist in elucidating the mechanisms of brain injury after intracerebral hemorrhage (ICH). However, almost all commercially available transgenic or knockout animals are mice. The purpose of this study was to develop an ICH model in mice and to investigate the influence of gender and complement C5 genetic differences on outcome after ICH. Male and female C57BL/6 mice and C5-deficient and -sufficient control mice were anesthetized and then received an injection of 30 μL autologous whole blood into the right basal ganglia. Brain water content was studied at 1 and 3 days after ICH. Behavioral tests (forelimb use asymmetry and corner turn test) were performed at 1, 3, 7, 14, 21, or 28 days after ICH. In male mice, brain water content was significantly increased in the ipsilateral basal ganglia 1 and 3 days after ICH, compared with saline injection controls ( P>0.01). There were marked neurological deficits 1 and 3 days after ICH, with progressive recovery over 28 days. In contrast, although brain edema and behavioral deficits were similar at 1 day after ICH in female and male mice, female mice showed reduced edema at 3 days and a faster recovery of behavioral deficits after ICH. 17β-estradiol treatment in male mice markedly reduced ICH-induced edema ( P>0.01). Brain water content was significantly increased in C5-deficient mice compared with C5-sufficient at 3 days after ICH ( P>0.05). These findings suggest that the mouse ICH model is a reproducible and feasible model. These results also suggest that gender and complement C5 are factors affecting brain injury after ICH.