Angiogenesis therapy against cerebral ischemic disease

血管生成治疗脑缺血性疾病

• 批准号: 17591521
• 负责人: KOBAYASHI Hidenori
• 金额: $ 2.28万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591521/
• 关键词: HIF-1 α; Cerebral Infarction; VEGF; Ischemic Tolerance; GGA; HSP-70; Angiogenesis; Hypoxia; HIF-1; HSP70

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.

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。

项目成果

Geranylgeranylacetone,a noninvasive heat shock protein inducer,induces protein kinase C and leads to neuroprotection against cerebral infarction in rats

香叶基香叶基丙酮是一种非侵入性热休克蛋白诱导剂，可诱导蛋白激酶 C 并导致大鼠脑梗塞的神经保护作用

• 发表时间: 2006
• 期刊: Neurosci Lett 396
• 作者: Akagawa H;Kasuya H;et al.;Kasuya et al.;Fujiki M;Uchida S
• 通讯作者: Uchida S

Geranylberanylacetone, a noninvasive heat shock protein inducer induces protein kinase C and leads to neuroprotection against cerebral infarction in rats.

Geranylberanylacetone 是一种非侵入性热休克蛋白诱导剂，可诱导蛋白激酶 C，从而对大鼠脑梗塞产生神经保护作用。

• 发表时间: 2006
• 期刊: Neurosci Lett 396・3
• 作者: Anan;M.;Abe;T.;Matsuda;T.;Ishii;K.;Kamida;T.;Fujiki;M.;Kobayashi;H.;阿部竜也;Fujiki M;Fujiki M;Hashimoto S;Fujiki M;Anan M;Uchida S
• 通讯作者: Uchida S

Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment

• DOI: 10.1016/j.neulet.2006.07.005
• 发表时间: 2006-09-25
• 期刊: NEUROSCIENCE LETTERS
• 影响因子: 2.5
• 作者: Fujiki, Minoru;Hikawa, Takarnitsu;Kobayashi, Hidenori
• 通讯作者: Kobayashi, Hidenori

血管新生研究と脳神経外科治療への展開

血管生成研究和神经外科治疗的进展

• 发表时间: 2006
• 期刊: 脳神経外科 34
• 作者: Akagawa H;Tajima A;Sakamoto Y;Krischek B;Yoneyama T;Kasuya H 他;Morishige M;阿部 竜也
• 通讯作者: 阿部 竜也

Induced angiogenesis under cerebral ischemia by cyclo-oxygenase 2 and hypoxia-inducible factor naked DNA in a To indirect-bypass model

To 间接旁路模型中环加氧酶 2 和缺氧诱导因子裸 DNA 诱导脑缺血下血管生成

• 发表时间: 2006
• 期刊: Neurosci Lett 409(2)
• 作者: Anan;M.;Abe;T.;Matsuda;T.;Ishii;K.;Kamida;T.;Fujiki;M.;Kobayashi;H.
• 通讯作者: H.