Over-expression of Slit2 induces vessel formation and changes blood vessel permeability in mouse brain.
Over-expression of Slit2 induces vessel formation and changes blood vessel permeability in mouse brain.
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DOI：
10.1038/aps.2011.106
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发表时间：
2011-11
影响因子：
8.2
通讯作者：
Geng JG
中科院分区：
文献类型：
--
作者：
Han HX;Geng JG
研究轴突导向因子Slit 2对小鼠脑内血管密度和血脑屏障通透性的影响。构建Slit 2转基因小鼠品系，并根据侧脑室（LV）、脑室压力和脉络丛比较小鼠的表型。使用体内Miles渗透性测定和淀粉样蛋白-β渗透性测定来评估脑中血管的渗透性。建立脑血管铸型和脑出血模型，观察转基因小鼠脑血管密度的变化。采用体外渗透性试验检测Slit 2是否能改变血管内皮细胞的渗透性和紧密连接。部分转基因小鼠出现脑积水，侧脑室面积增大，脑室压升高。转基因小鼠的脉络丛结构也发生了变化，微血管增多，血管扩张，上皮细胞和内皮细胞之间有间隙。Slit 2改善了脑血管密度，也增加了脑血管对大分子的渗透性。这些血管对诱发脑出血的线索也更敏感。在细胞水平，Slit 2扰乱了血管内皮细胞紧密连接的完整性，并改善了内皮细胞层的通透性。因此，它促进淀粉样β肽从血清进入中枢神经系统，在那里它们与神经元结合。Slit 2改善转基因小鼠脑中的血管密度和通透性。因此，Slit 2诱导脑血管和屏障系统的许多变化。
To investigate the effect of the axon guidance cue Slit2 on the density of blood vessels in the mouse brain and the permeability of the blood-brain barrier. A Slit2 transgenic mouse line was constructed, and the phenotypes of the mice were compared according to the lateral ventricle (LV), ventricle pressure, and the choroids plexus. An in vivo Miles permeability assay and an amyloid-β permeability assay were used to assess the permeability of blood vessels in the brain. Then brain vessel casting and intracerebral hemorrhage models were built to investigate vessel density in the transgenic mice. An in vitro permeability assay was used to test whether Slit2 could change the permeability and tight junctions of blood vessel endothelial cells. Hydrocephalous occurred in some transgenic mice, and a larger lateral ventricle area and higher ventricle pressure were observed in the transgenic mice. The transgenic mice also displayed a change in the construction of the choroids plexus, which had more micro vessels, dilated vessels, gaps between epithelial cells and endothelial cells. Slit2 improved brain vessel density and also increased the permeability of brain vessels to large molecules. These blood vessels were also more sensitive to cues that induce brain hemorrhage. At the cellular level, Slit2 disturbed the integrity of tight junctions in blood vessel endothelial cells and improved the permeability of the endothelial cell layer. Thus, it promoted the entry of amyloid-β peptides from the serum into the central nervous system, where they bound to neurons. Slit2 improves vessel density and permeability in the brains of transgenic mice. Thus, Slit2 induces numerous changes in brain vessels and the barrier system.