Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage
Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage
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DOI：
10.1038/sj.jcbfm.9600354
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发表时间：
2007-03-01
影响因子：
6.3
通讯作者：
Lo, Eng H.
中科院分区：
文献类型：
--
作者：
Tejima, Emiri;Zhao, Bing-Qiao;Lo, Eng H.
我们检验了星形细胞基质金属蛋白酶- 9 （MMP- 9）介导出血性脑水肿的假设。在一个出血性中风的临床病例中，MMP- 9与血肿周围的星形细胞和神经元共定位。在纹状体注射血液的小鼠模型中，MMP- 9与出血病变周围的星形胶质细胞共定位。由于MMP- 9既存在于血液中，也存在于大脑中，我们比较了野生型（WT）和MMP- 9敲除型（KO）小鼠的四组：注入WT脑的WT血，注入KO脑的KO血，注入KO脑的WT血，注入KO脑的WT血和注入WT脑的KO血。凝胶酶谱分析显示，MMP- 9在WT型脑组织中表达升高，而在KO型脑组织中表达缺失。将WT血注入WT脑后，水肿水含量升高。然而，当MMP- 9在血液或大脑或两者中缺失时，水肿得到改善。为了进一步评估MMP- 9诱导星形细胞的机制，我们接下来检测了小鼠原代星形细胞培养。在条件培养基中暴露于血红蛋白1至24小时内，MMP- 9迅速上调。血红蛋白诱导的MMP- 9被自由基清除剂U83836E减少。综上所述，这些数据表明，尽管血液中存在大量的MMP- 9，但血红蛋白诱导的氧化应激可触发星形胶质细胞中的MMP- 9，这些基质降解的实质来源也可能是出血性脑水肿发病的重要因素。
We tested the hypothesis that astrocytic matrix metalloproteinase- 9 ( MMP- 9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP- 9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP- 9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP- 9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP- 9 knockout ( KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP- 9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP- 9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP- 9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP- 9 in conditioned media within 1 to 24 h. Hemoglobin- induced MMP- 9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP- 9 in blood, hemoglobin- induced oxidative stress can trigger MMP- 9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema.