CEREBRAL ISCHEMIA AND EXPRESSION OF STRESS GENES

描述：(改编自申请人的摘要)：提案希望 确定应激基因的表达是否起重要作用 对脑缺血后细胞存活的影响。该提案将重点放在 编码主要诱导物70的HSP-70mRNA的表达 千道尔顿热休克蛋白。将使用原位杂交技术 检测缺血后HSP-70mRNA的表达。可逆的 采用大鼠局灶性脑缺血模型。这就产生了 大脑中动脉范围内的皮质梗塞。这个 具体目标是：(1)确定时间顺序和区域表达 原位研究大鼠局灶性脑缺血后热休克蛋白-70基因的表达 杂交，并将这种表达与区域范围相关联 组织学损伤；(2)确定预先诱导HSP-70是否 保护脑组织免受随后一段时间的缺血； 确定一种已知的保护剂亚低温是否会改变 局灶性脑缺血后热休克蛋白-70的表达；(4)确定脑缺血是否增强 其他应激相关基因(c-fox、HSP-90、泛素、 葡萄糖调节蛋白，鸟氨酸脱羧酶)，原位使用 杂交和(5)确定HSP-70的表达是否增强 高能磷酸盐和/或AN的减少触发了信使核糖核酸 在缺血性损伤过程中乳酸水平升高。

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.