CEREBRAL ISCHEMIA AND EXPRESSION OF STRESS GENES

脑缺血和应激基因的表达

• 批准号: 3416110
• 负责人: FRANK A WELSH
• 金额: $ 14.44万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3416110
• 关键词: cell death; cerebral ischemia /hypoxia; gene expression; high energy compound; hypothermia; in situ hybridization; laboratory rat; lactates; messenger RNA; radiotracer; reperfusion; stress proteins

DESCRIPTION: (Adapted from the Applicant's abstract): The proposal hopes to determine whether the expression of stress genes play an important role in cell survival following cerebral ischemia. The proposal will focus on the expression of HSP-70 mRNA, which codes for the major inducible 70 kilodalton heat shock protein. In situ hybridization will be used to detect the expression of HSP-70 mRNA following ischemia. A reversible model of focal ischemia in rat brain will be employed. This produces cortical infarction in the territory of the middle cerebral artery. The specific aims are to: (1) determine the timecourse and regional expression of HSP-70 mRNA following focal ischemia in rat brain using in situ hybridization, and correlate this expression with the regional extent of histological injury; (2) to determine whether prior induction of HSP-70 protects brain tissue against a subsequent period of ischemia; (3) to determine whether a known protectant, hypothermia, alters the expression of HSP-70 following focal ischemia; (4) to determine whether ischemia enhances the expression of other stress-related genes (c-fox, HSP-90, ubiquitin, glucose-regulated protein, ornithine decarboxylase), using in situ hybridization and (5) to determine whether enhanced expression of HSP-70 mRNA is triggered by a decrease in high-energy phosphates and/or an increase in lactate during the ischemic insult.

描述：（改编自申请人摘要）：该提案希望 以确定是否胁迫基因的表达发挥重要作用 脑缺血后细胞存活率的变化 该提案将侧重于 HSP-70 mRNA的表达，其编码主要的可诱导的70 热休克蛋白 原位杂交将用于 检测缺血后HSP-70 mRNA的表达。 可逆 将使用大鼠脑中的局灶性缺血模型。 这产生 大脑中动脉区域的皮质梗死。 的 具体目标是：（1）确定时间进程和区域表达 大鼠局灶性脑缺血后HSP-70 mRNA的原位表达 杂交，并将这种表达与区域范围相关， 组织学损伤;（2）确定是否预先诱导HSP-70 保护脑组织免受随后的缺血期;（3） 确定一种已知的保护剂，低温，是否改变了 HSP-70在局灶性缺血后的变化;（4）确定缺血是否增强了HSP-70在局灶性缺血后的表达。 其它应激相关基因（c-fox，HSP-90，泛素， 葡萄糖调节蛋白，鸟氨酸脱羧酶），使用原位 杂交和（5）确定是否增强HSP-70的表达 mRNA是由高能磷酸盐和/或磷酸盐的减少触发的 缺血性损伤期间乳酸盐增加。