SPINAL NEURAL ACTIVITY--ROLE IN POST ISCHEMIC INJURY

描述：（改编自申请人摘要）本次修订后的续展 建议是调查某些干预措施的机制， 保护免受一段时间后的一连串有害事件的影响， 脊髓缺血 有两个具体目标。 第一个是定义 最佳的温度和时间特性的缺血冷却。 缺血后果或保护相关变化的测量 包括脊髓细胞外钾、背角神经元活性、氨基 酸和PGE 2释放，2-5天时的神经学结局和脊髓 组织病理学 第二个目的是确定影响脊髓损伤的因素， HSP 72和立即早期基因的表达及其相关性 表达与缺血后功能恢复。 hsp72、c-fos和c-jun 将在瞬时冷却或加热到两个温度后测量表达 不同的温度，鞘内递送P物质; NMDA，AMPA，或 红藻氨酸;高钾;或两种短暂的非伤害性 脊髓缺血的时间间隔。 这些手法的保护作用 将根据观察到的损害进行测量， 在预处理后以3个不同的时间间隔递送缺血 诱导hsp 72和/或fos/jun表达的处理; 包括神经学结果、脊髓氨基酸和PGE 2释放， 组织病理学 HSP 72表达在保护中的作用将被测试。 通过检测反义预处理对HSP 72表达的影响， 缺血性损伤的三个指标

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.