Shin Yoo-Jin, Choi Jeong-Sun, Lee Ji-Yeon, Choi Jae-Youn, Cha Jung-Ho, Chun Myung-Hoon, Lee Mun-Yong
Department of Anatomy, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
Acta Neuropathol. 2008 Nov;116(5):517-27. doi: 10.1007/s00401-008-0423-x. Epub 2008 Aug 15.
We investigated the changes in the expression of vascular endothelial growth factor-C (VEGF-C) and its receptor, VEGFR-3, in the rat hippocampus following transient forebrain ischemia. The expression profiles of VEGF-C and VEGFR-3 were very similar in the control hippocampi, where both genes were constitutively expressed in neurons in the pyramidal cell and granule cell layers. The spatiotemporal expression pattern of VEGF-C was similar to that of VEGFR-3 in the ischemic hippocampus, and in the CA1 and dentate hilar regions both VEGF-C and VEGFR-3 were strongly expressed in activated glial cells rather than in neurons. Most of the activated glial cells expressing both genes were reactive astrocytes, although some were a subpopulation of brain macrophages. In the dentate gyrus, however, VEGFR-3 expression was transiently increased in the innermost layer of granule cells on days 7-10 after reperfusion, coinciding with an increase in polysialylated neural cell adhesion molecule staining--a marker for immature neurons. These data suggest that VEGF-C may be involved in glial reaction via paracrine or autocrine mechanisms in the ischemic brain and may carry out specific roles in adult hippocampal neurogenesis during ischemic insults.
我们研究了短暂性前脑缺血后大鼠海马中血管内皮生长因子-C（VEGF-C）及其受体VEGFR-3的表达变化。在对照海马中，VEGF-C和VEGFR-3的表达谱非常相似，这两个基因在锥体细胞层和颗粒细胞层的神经元中组成性表达。在缺血海马中，VEGF-C的时空表达模式与VEGFR-3相似，在CA1区和齿状门区，VEGF-C和VEGFR-3均在活化的胶质细胞中强烈表达，而非在神经元中。大多数表达这两个基因的活化胶质细胞是反应性星形胶质细胞，尽管有些是脑巨噬细胞亚群。然而，在齿状回中，再灌注后7-10天，颗粒细胞最内层的VEGFR-3表达短暂增加，这与多唾液酸化神经细胞粘附分子染色增加一致，多唾液酸化神经细胞粘附分子是未成熟神经元的标志物。这些数据表明，VEGF-C可能通过旁分泌或自分泌机制参与缺血性脑内的胶质反应，并可能在缺血性损伤期间的成年海马神经发生中发挥特定作用。
