SPINAL NEURAL ACTIVITY--ROLE IN POST ISCHEMIC INJURY

描述：(改编自申请人的摘要)本修订后的续期 建议是调查某些干预措施的机制 防范在一段时间内发生的一连串有害事件 脊髓缺血。有两个具体目标。第一种方法是定义 全脑缺血降温的最佳温度和时间特征。 衡量缺血后果或与保护相关的变化 包括脊髓细胞外钾、背角神经元活动、氨基酸 酸和前列腺素E_2的释放、2-5天的神经转归和脊髓 组织病理学。第二个目标是定义支配脊椎的因素 热休克蛋白72和即刻早期基因的表达及其相关性 表达与缺血后功能恢复有关。HSP72、c-fos和c-jun 在瞬时冷却或加热到两个小时后，将测量表情 不同温度，鞘内给药P物质；NMDA、AMPA或 红藻氨酸；高钾；或两种短暂的无害的 间歇性脊髓缺血。这些操作的保护效果 将根据观察到的损害来衡量，其固定的损害持续时间为 条件化后3个不同时间间隔出现缺血 诱导HSP72和/或FOS/JUN表达的处理；损害的测量 包括神经学结果、脊髓氨基酸和PGE2释放以及 组织病理学。HSP72的表达在保护中的作用将被测试 通过检测反义预处理对HSP72表达和HSP72基因表达的影响 同样的三个衡量缺血损伤的指标。

DESCRIPTION: (Adapted from the applicant's abstract) This revised renewal proposal is to investigate the mechanisms by which certain interventions protect against the cascade of deleterious events that follow a period of spinal ischemia. There are two specific aims. The first is to define the optimal thermal and temporal characteristics of perischemic cooling. Measures of ischemic consequences or correlative changes with protection include spinal extracellular potassium, dorsal horn neuronal activity, amino acid and PGE2 release, neurological outcome at 2-5 days and spinal histopathology. The second aim is to define the factors governing spinal expression of HSP72 and immediate early genes, and the correlation of such expression with post-ischemia functional recovery. hsp72, c-fos and c-jun expression will be measured following transient cooling or heating to two different temperatures, intrathecal delivery of substance P; NMDA, AMPA, or kainic acid; high potassium; or either of two transient non-injurious intervals of spinal ischemia. The protective effects of these manipulations will be measured on damage observed with a fixed injurious duration of ischemia delivered at 3 different intervals after the conditioning treatments which induce hsp72 and/or fos/jun expression; measures of damage include neurologic outcome, spinal amino acid and PGE2 release and histopathology. The role of HSP72 expression in protection will be tested by examining the effects of antisense pretreatment on HSP72 expression and the same three measures of ischemic damage.