The dynamics of revascularization after white matter infarction monitored in Flt1-tdsRed and Flk1-GFP mice
The dynamics of revascularization after white matter infarction monitored in Flt1-tdsRed and Flk1-GFP mice
复制标题
DOI：
10.1016/j.neulet.2018.10.057
复制
发表时间：
2019-01
影响因子：
2.5
通讯作者：
Hiroya Shimauchi-Ohtaki;M. Kurachi;M. Naruse;K. Shibasaki;Shouta Sugio;Ken Matsumoto;M. Ema;Y. Yoshimoto;Y. Ishizaki
中科院分区：
文献类型：
--
作者：
Hiroya Shimauchi-Ohtaki;M. Kurachi;M. Naruse;K. Shibasaki;Shouta Sugio;Ken Matsumoto;M. Ema;Y. Yoshimoto;Y. Ishizaki
皮质下白色物质梗塞由于血流紊乱而引起缺血性脱髓鞘和脑功能丧失。虽然血管新生是脑梗死后的恢复过程之一，但白色物质梗死后血管重建的动力学仍不清楚。我们通过注射血管收缩肽内皮素-1（ET-1）和一氧化氮合酶抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）诱导Flk 1-GFP：：Flt 1-tdsRed双转基因小鼠内囊白色梗死，并跟踪梗死区血管系统Flk 1和Flt 1表达的变化。注射后1天Flt 1-tdsRed阳性血管的减少和注射后3天Flk 1-GFP强阳性血管的增加明显。PDGFRβ-强阳性（PDGFRβ+）细胞在注射后3d出现于梗死区，此后数量增加。注射后三天，这些细胞中的大多数与Flk 1-GFP阳性内皮细胞紧密接触，表明这些细胞是真正的周细胞。注射后7天，PDGFRβ+细胞数量急剧增加，这些细胞中的绝大多数与Flk 1-GFP阳性内皮细胞没有紧密接触。总之，我们的研究结果表明，缺血损伤后早期血管再生开始，新生的周细胞首先包裹血管，然后产生与血管不直接相关的成纤维细胞样细胞。
Subcortical white matter infarction causes ischemic demyelination and loss of brain functions, as the result of disturbances of the blood flow. Although angiogenesis is one of the recovery processes after cerebral infarction, the dynamics of revascularization after white matter infarction still remains unclear. We induced white matter infarction in the internal capsule of Flk1-GFP::Flt1-tdsRed double transgenic mice by injection of endothelin-1 (ET-1), a vasoconstrictor peptide, together with N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and followed the changes in Flk1 and Flt1 expression in the vascular system in the infarct area. Reduction of Flt1-tdsRed-positive blood vessels 1 day after the injection and increase of Flk1-GFP-strongly-positive blood vessels 3 days after the injection were apparent. PDGFRβ-strongly-positive (PDGFRβ+) cells appeared in the infarct area 3 days after the injection and increased their number thereafter. Three days after the injection, most of these cells were in close contact with Flk1-GFP-positive endothelial cells, indicating these cells are bona fide pericytes. Seven days after the injection, the number of PDGFRβ+ cells increased dramatically, and the vast majority of these cells were not in close contact with Flk1-GFP-positive endothelial cells. Taken together, our results suggest revascularization begins early after the ischemic insult, and the emerging pericytes first ensheath blood vessels and then produce fibroblast-like cells not directly associated with blood vessels.