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：（根据申请人的摘要改编）：提案希望 确定压力基因的表达是否起重要作用 在脑缺血后的细胞存活中。 该提议将重点放在 HSP-70 mRNA的表达，该mRNA编码为主要诱导70 千瓦尔顿热休克蛋白。 原位杂交将用于 检测缺血后HSP-70 mRNA的表达。 可逆的 将采用大鼠大脑中局灶性缺血模型。 这会产生 大脑中部动脉领土的皮质梗塞。 这 具体目的是：（1）确定时间和区域表达 使用原位的HSP-70 mRNA在大鼠脑中局灶性缺血后 杂交，并将这种表达与区域范围相关联 组织学损伤； （2）确定是否先前诱导HSP-70 保护脑组织免受随后的缺血时期； （3）到 确定已知的保护剂，体温过低是否改变了表达 局灶性缺血之后的HSP-70； （4）确定缺血是否增强 其他与应激相关基因的表达（C-Fox，HSP-90，泛素， 葡萄糖调节的蛋白质，鸟氨酸脱羧酶），使用原位 杂交和（5）确定是否增强了HSP-70的表达 mRNA是由高能磷酸盐和/或A的降低而触发的 缺血性损伤期间乳酸的增加。