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脑出血后骨桥蛋白介导神经母细胞持续从脑室下区迁移至损伤的纹状体。

Persistent migration of neuroblasts from the subventricular zone to the injured striatum mediated by osteopontin following intracerebral hemorrhage.

作者信息

Yan Yi-Ping, Lang Bradley T, Vemuganti Raghu, Dempsey Robert J

机构信息

Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.

出版信息

J Neurochem. 2009 Jun;109(6):1624-35. doi: 10.1111/j.1471-4159.2009.06059.x. Epub 2009 Mar 25.

Abstract

We investigated intracerebral hemorrhage (ICH)-induced lateral migration of neuroblasts and the mechanism underlying this migration. ICH model was induced by collagenase injection into the striatum of adult wild-type and osteopontin (OPN) knockout mice. In the wild-type mice, the lateral migration of neuroblasts from the ipsilateral subventricular zone (SVZ) towards the hematoma started at day 3 and continued up to day 28 after ICH. In addition to migrating towards the hematoma, neuroblasts also migrated to the area of ipsilateral striatum remote to the hematoma. The migrating neuroblasts were closely associated with activated astrocytes and blood vessels in the injured striatum. Following ICH, the expression of OPN was up-regulated in the ipsilateral striatum from day 1 to day 28. In vitro, OPN treatment did not affect the proliferation of neural progenitors, but enhanced the trans-well and radial migration of neural progenitors. In vivo, OPN deficiency did not affect the proliferation of neural progenitors in the SVZ. However, following ICH a significant decrease in lateral neuroblast migration was observed in the OPN knockout mice compared with the wild-type mice. These results suggest that increased OPN expression in the injured striatum plays a significant role in the lateral migration of neuroblasts following ICH.

摘要

我们研究了脑出血(ICH)诱导的神经母细胞侧向迁移及其迁移机制。通过向成年野生型和骨桥蛋白(OPN)基因敲除小鼠的纹状体内注射胶原酶建立ICH模型。在野生型小鼠中,神经母细胞从同侧脑室下区(SVZ)向血肿的侧向迁移在ICH后第3天开始,并持续至第28天。除了向血肿迁移外,神经母细胞还迁移至同侧纹状体远离血肿的区域。迁移的神经母细胞与受损纹状体内活化的星形胶质细胞和血管密切相关。ICH后,同侧纹状体内OPN的表达从第1天至第28天上调。在体外,OPN处理不影响神经祖细胞的增殖,但增强了神经祖细胞的Transwell迁移和径向迁移。在体内,OPN缺乏不影响SVZ中神经祖细胞的增殖。然而,与野生型小鼠相比,ICH后OPN基因敲除小鼠的神经母细胞侧向迁移显著减少。这些结果表明,受损纹状体内OPN表达的增加在ICH后神经母细胞的侧向迁移中起重要作用。

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