Augmented delayed infarct expansion and reactive astrocytosis after permanent focal ischemia in apolipoprotein E4 knock-in mice
Augmented delayed infarct expansion and reactive astrocytosis after permanent focal ischemia in apolipoprotein E4 knock-in mice
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DOI：
10.1097/01.wcb.0000120787.53851.a4
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发表时间：
2004-06-01
影响因子：
6.3
通讯作者：
Asano, T
中科院分区：
文献类型：
--
作者：
Mori, T;Town, T;Asano, T
使用纯合子人载脂蛋白E2（apoE 2）（2/2）-、apoE 3（3/3）-。或apoE 4（4/4）-敲入（KI）小鼠，我们旨在检查永久性大脑中动脉闭塞（pMCAO）后是否发生apoE亚型特异性的迟发性梗死扩展加重。与2/2-或3/3-KI小鼠相比，4/4-KI小鼠在pMCAO后表现出明显更大的梗死体积和更严重的神经功能缺损，后两组之间无显著差异。pMCAO后1 ~ 5天，4/4-KI小鼠的脑体积显著增加。而在2/2-或3/3-KI小鼠中没有显著改变。通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸-缺口末端标记检测到的梗死周围区域的DNA片段化在pMCAO后5天在所有KI小鼠中增加到相似的程度，小鼠组之间没有显著差异。在每个时间点检查，人载脂蛋白E是最显着的表达在梗死周围地区，具有类似的免疫反应性之间的三个线的KI小鼠。在4/4-KI小鼠中，梗死周围区域的胶质细胞酸性蛋白免疫反应性负荷在7天内逐渐增加，但在2/2-或3/3-KI小鼠中则没有。总之，这些数据表明apoE 4同种型在基因工程apoE-KI小鼠中pMCAO的亚急性期加重延迟性梗死扩展和梗死周围反应性星形细胞增多。
Using homozygous human apolipoprotein E2 (apoE2) (2/2)-, apoE3 (3/3)-. or apoE4 (4/4)-knock-in (KI) mice, we aimed to examine whether an apoE isoform-specific exacerbation of delayed infarct expansion occurs after permanent middle cerebral artery Occlusion (pMCAO). Compared with 2/2- or 3/3-KI mice, 4/4-KI mice exhibited significantly larger infarct volumes and worse neurologic deficits after pMCAO, with no significant differences between the latter two groups. Infarct volume in 4/4-KI mice was significantly increased from 1 to 5 days after pMCAO. whereas that in 2/2- or 3/3-KI mice was not significantly altered. DNA fragmentation in the peri-infarct area as detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end-labeling was increased to a similar degree in all of the KI mice by 5 days after pMCAO, with no significant differences among the mouse groups. At every time-point examined, human apoE was most markedly expressed in the peri-infarct area, with similar immunoreactivity among the three lines of KI mice. The glial fibrillary acidic protein immunoreactive burden in the peri-infarct area was progressively increased through 7 days in 4/4-KI mice, but not in 2/2- or 3/3-KI mice. Taken together, these data show that the apoE4 isoform acts to aggravate delayed infarct expansion and peri-infarct reactive astrocytosis during the subacute phase of pMCAO in genetically engineered apoE-KI mice.