SPINAL NEURAL ACTIVITY--ROLE IN POST ISCHEMIC INJURY

继发于主动脉闭塞的短暂性脊髓缺血可诱导 脊髓功能障碍由于侧支血流，脊髓灌注福尔斯 在闭塞后达到非常低的水平，并且该水平逐渐被 时间，导致明显的不可逆的功能丧失。的失败 功能可以归因于三个主要变量：i）渐进损失 ii）代谢底物的供应与细胞代谢底物的供应之间的不匹配 需要和iii）释放神经递质，如谷氨酸， 用于增加神经元活性和增加细胞内钙。 升高的钙激活许多细胞内酶，包括 磷脂酶，产生花生四烯酸和随之而来的增加 前列腺素类前列腺素类对神经元释放具有强大的作用， 也表明作为结果形成的自由基的形成， 环氧合酶的作用。我们感兴趣的是， 递质释放，酶促过程和能量需求事件 该电池显示出高度的温度依赖性。这种依赖性可以 说明冷却对保持回流焊后功能的功效。 定量评估大范围温度对 脊髓递质释放，脊髓代谢率，脊髓血流量 通过行为和系统性组织病理学评估， 建立这几个变量与 回流焊后图片的演变。目前的数据显示， 这是可能的分离的温度敏感性的脊髓 谷氨酸、牛磺酸和TXB 2释放。这些研究将在 用一个简单的，特征良好的大鼠模型， 使用从股动脉穿过的2F Fogarty导管实现闭塞 动脉，通过鞘内导管输送脊髓药物，脊髓 用微透析导管研究递质释放;脊髓血 使用激光多普勒测量血流;以及，脊髓葡萄糖利用率 使用2-脱氧葡萄糖评估。这些实验的结果将 具体涉及以下几个问题：i） 暴露于常温缺血和神经和 组织病理学变化，ii）递质释放的协方差 （谷氨酸、牛磺酸和TXB 2）、脊髓葡萄糖利用和脊髓 血流量与神经功能缺损和脊髓组织病理学作为一个 在维持脐带的同时进行主动脉闭塞的后果 在29至40摄氏度的温度下短暂缺血期间或之后; iii）是否外源性增加神经元活性（如鞘内注射）， NMDA或K+）增加短暂缺血后神经元的脆弱性 以及iv）是否阻断脊髓NMDA和非NMDA受体位点 产生一个节省的效果，以及这种效果是否在 存在缺血周围脊髓体温过低。从实际 从这个角度来看，这些研究将系统地解决几个问题， 我们认为有临床影响：l）是否更深的低温赋予 逐步加强保护，这是一种反映问题的权衡， 与深低温相关，2）低温在 缺血间隔与缺血后（当代谢减少时） 活动可能会延迟体内平衡的恢复）和3）内- 缺血性再流间期对预后的影响。

Transient spinal cord ischemia secondary to aortic occlusion can induce spinal dysfunction. Because of collateral flow, spinal perfusion falls after occlusion to a very low level and this level gradually worsens with time, leading to an apparent irreversible loss of function. The failure of function may be ascribed to three principle variables: i) progressive loss of flow, ii) mismatch between supply of metabolic substrates and cellular requirements and iii) release of neurotransmitters, such as glutamate that serve to increase neuronal activity and to increase intracellular calcium. The elevated calcium activates a number of intracellular enzymes including phospholipase which yields arachidonic acid and a consequent increase in prostanoids. Prostanoids have powerful effects upon neuronal release and also signal the formation of free radicals formed as a consequence of the action of cyclooxygenase. Of interest to us is the fact that both transmitter release, enzymatic process and energy-requiring events within the cell show a high degree of temperature dependency. Such dependency may account for the efficacy of cooling on preserving post reflow function. Quantitative assessment of the effect of a broad range of temperatures on spinal transmitter release, spinal metabolic rate, spinal cord blood flow and outcome, as assessed by behavior and systematic histopathology would establish the potential relationship of these several variables to the evolution of the post reflow picture. Current data has already indicated that it is possible to dissociate the temperature sensitivity of spinal glutamate, taurine and TXB2 release. These studies will be accomplished with a simple, well characterized rat model where reversible aortic occlusion is achieved with a 2F Fogarty catheter passed from the femoral artery, with spinal drugs delivered by an intrathecal catheter, spinal transmitter release studied with a microdialysis catheter; spinal blood flow measured using laser Doppler; and, spinal glucose utilization assessed using 2-deoxyglucose.The results of these experiments will specifically address several issues: i) correlation between time of exposure to normothermic ischemia and degree of neurological and histopathological changes, ii) covariance of transmitter release (glutamate, taurine and TXB2), spinal glucose utilization, and spinal cord blood flow with neurological deficit and spinal histopathology as a consequence of aortic occlusion carried out while the cord is maintained during or after transient ischemia at temperatures of 29 to 40 degrees C; iii) whether exogenously increased neuronal activity (as with intrathecal NMDA or K+) increases neuronal vulnerability after short lasting ischemia and, iv) whether blockade of spinal NMDA and non-NMDA receptor sites produce a sparing effects and whether this effect is augmented in the presence of periischemic spinal cord hypothermia. From a practical standpoint, these studies will systematically address several points which we think have clinical impact: l) whether deeper hypothermia confers progressively greater protection, a trade off reflecting the problems associated with deep hypothermia, 2) importance of hypothermia during the ischemic interval versus following ischemia (when decreased metabolic activity may delay recovery of homeostasis) and 3) the benefit of intra- ischemic intervals of reflow on outcome.