Gene therapy for cerebral vasosposm (Basic research for gene trans fer to cerebral blood vessels)

脑血管痉挛的基因治疗（基因转移至脑血管的基础研究）

基本信息

批准号：
10671326
负责人：
KASUYA Hidetoshi
金额：
$ 1.92万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671326/
关键词：
subarachnoid hemorrhage cerebral rasospasm gene gene expression gene therapy 炎症ベクター

项目摘要

Vasospasm remains a major cause of morbidity and mortality after subarachnoid hemorrhage. Some therapeutic approaches are promising, but none has been shown completely ameliorate vasoapsm or the ischemic deficit associated with vasospasm. Gene therapy may be useful for prevention or treatment of cerebral vasospasm. (1) NF-kB decoy with cationic liposome as vector was injected into cisterna magna in canine double hemorrhage model. Cerebral vasospasm was not reversed by NF-kB decoy. Fluorescence-labeled decoy was successfully transfected into not only cerebral vessels but brain parenchyma. Single injection of NF-kB cationic liposome may not be used for gene transfer to cerebral blood vessels in the presence of cisternal blood. (2) Drug delivery system for the selective transfection to cerebral vessels may be needed to prevent vasospasm. (3) We investigated the changes of gene expressions in the spastic artery using differential display, DNA array, and TaqMan technology. Genes related to inflammation such as cytokines were expressed extensively in the spastic artery, suggesting that gene therapy to suppress inflammation may be useful.

血管痉挛仍然是蛛网膜下腔出血后发病率和死亡率的主要原因。一些治疗方法是有希望的，但是没有显示完全改善血管aPSM或与血管痉挛相关的缺血性赤字。基因治疗可能有助于预防或治疗脑血管痉挛。（1）将带有阳离子脂质体的NF-KB诱饵注入了犬双出血模型中的甲壳虫含量。 NF-KB诱饵不会逆转大脑血管痉挛。荧光标记的诱饵不仅被成功地转染到脑血管，而且转染到脑实质中。在脑海中存在的情况下，单一注射NF-KB阳离子脂质体不得用于基因转移至脑血管。（2）可能需要向脑血管进行选择性转染的药物输送系统以防止血管痉挛。（3）我们使用差分显示，DNA阵列和Taqman技术研究了痉挛性动脉中基因表达的变化。与炎症有关的基因（例如细胞因子）在痉挛性动脉中广泛表达，这表明抑制炎症的基因治疗可能是有用的。