Decreased brain edema after collagenase-induced intracerebral hemorrhage in mice lacking the inducible nitric oxide synthase gene: Laboratory investigation

Abstract

Object. Hematoma size and brain edema after intracerebral hemorrhage (ICH) are important prognostic factors. Inducible nitric oxide synthase (iNOS) is induced after cerebral ischemia and is known to be involved in secondary neuronal injury, but its significance in ICH is unknown. The authors tested whether iNOS would influence hematoma size and brain edema after ICH. Methods. The authors used C57BL/6 and iNOS knockout mice for all the experiments. Experimental ICH was induced by the intrastriatal stereotactic administration of bacterial collagenase. Brain tissue was obtained at 72 hours after ICH. The volume of hematoma was quantified by spectrophotometric assay, and the brain water content was measured. The investigators also measured blood-brain barrier permeability using Evans blue dye. Results. There was no significant difference in hematoma size between the 2 groups. The brain water content of the lesional hemisphere was higher in C57BL/6 mice than in iNOS knockout mice. More Evans blue leakage in the brain was observed in C57BL/6 control mice than in iNOS knockout mice. Immunohistochemistry showed iNOS immunoreactivity in the perihematoma areas of C57BL/6 mice but not in the iNOS knockout mice. Conclusions. When hematoma size was similar, iNOS knockout mice had significantly less brain edema than their littermates. These results suggest that iNOS modulation might become an antiedematous therapy for ICH.