Angiogenesis therapy against cerebral ischemic disease

低氧诱导因子1（HIF-1）是一种调节哺乳动物细胞低氧适应性反应的转录因子。它由调节亚基HIF-1α和组成型表达亚基HIF-1β组成。我们研究了HIF-1α裸DNA在体内脑缺血模型中诱导的血管生成。我们利用大鼠脑-肌-血管结合模型，将HIF-1α裸DNA接种于脑表面或颞肌。分析HIF-1α诱导的血管生成因子和侧支循环。与对照组相比，HIF-1α DNA处理的组织切片显示HIF-1α和VEGF的表达增加。HIF-1α转录因子能够促进显著的血管生成。本研究旨在探讨银杏叶提取物对大鼠大脑中动脉（MCA）永久性闭塞所致脑梗死的保护作用。缺血前48 h单次口服GGA（800 mg/kg）可明显缩小脑梗死体积。一个显着增加HSP 70的免疫反应性被发现在新皮质在GGA治疗的动物有或无缺血。单次口服GGA预处理为探索脑缺血性神经元损伤的神经保护机制提供了重要工具。

Hyoxia-inducible factor 1(HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1α, which accumulates under hypmic conditions, and constitutively expressed subunit, HIF-1β. We investigated HIF-1α naked DNA-induced angiogenesis in a cerebral ischemic model in vivo. We utilized a rat encephalo-myo-synangiosis model and inoculated HIF-1α naked DNA on the brain surface or temporal muscle. We analyzed HIF-1α induced angiogenic factors and collateral circulation. A histological section treated with HIF-1α DNA showed an increased expression of HIF-1α and VEGF with collateral circulation, in comparison with control DNA HIF-1α transcription factor is able to promote significant angiogenesis development.Geranylgeranylacetone (GGA) is known as an antinuclear agent and more recently as a heat shock protein (HSP) inducer. This study evaluated the neuroprotective effect of GGA against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion in rats. GGA was given orally in various regimens prior to MCA ocdusion Pretreatment with a single oral GGAdose (800 mg/kg) 48 hours before ischemia significantly attenuated cerebral infarction volume. A significant increase in HSP70 immunoreactivity was found in the neocortex in GGA-treated animals with or without ischemia. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against cerebral ischemic neuronal damage.