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

Decreased brain edema after collagenase-induced intracerebral hemorrhage in mice lacking the inducible nitric oxide synthase gene
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DOI:
10.3171/2009.3.jns081285
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发表时间:
2009-11-01
影响因子:
4.1
通讯作者:
Jeong, Sang-Wuk
Jeong, Sang-Wuk
中科院分区:
医学1区
文献类型:
--
作者:
Kim, Dong Wook;Im, So-Hyang;Jeong, Sang-Wuk

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Object.脑出血后血肿大小和脑水肿是重要的预后因素。诱导型一氧化氮合酶(iNOS)在脑缺血后被诱导,已知其参与继发性神经元损伤,但其在ICH中的意义尚不清楚。作者测试了iNOS是否会影响ICH后的血肿大小和脑水肿。作者使用C57 BL/6和iNOS敲除小鼠进行所有实验。实验性脑出血是由纹状体内立体定向注射细菌胶原酶诱导的。在ICH后72小时获得脑组织。用分光光度法测定血肿体积,并测定脑含水量。研究人员还使用伊文思蓝染料测量了血脑屏障的通透性。两组之间的血肿大小无显著差异。C57 BL/6小鼠损伤半球脑组织含水量高于iNOS基因敲除小鼠。在C57 BL/6对照小鼠中观察到比iNOS敲除小鼠更多的脑中伊文思蓝渗漏。免疫组化显示C57 BL/6小鼠血肿周围区域有iNOS免疫反应阳性,但在iNOS敲除小鼠中没有。当血肿大小相似时,iNOS敲除小鼠的脑水肿明显少于同窝出生的小鼠。这些结果表明,iNOS的调制可能成为一种抗水肿治疗ICH。(DOI:10.3171/2009.3.JNS081285)
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. (DOI: 10.3171/2009.3.JNS081285)