FOCAL STROKE: METABOLISM AND PH USING NEUTRAL RED

这个项目的长期目标是确定组织酸的作用- 基础和代谢紊乱在脑梗塞后的演变中的作用 局灶性中风。实验性局灶性脑缺血与大多数人类更相关 笔画比全球模型更多。从震源模型获得的信息 然而，由于脑缺血的变异性，缺血的发生一直令人沮丧 现有模型中病变的大小和位置。 中期后缺血灶周围血流减少的区域 大脑动脉(MCA)闭塞显然可以在最初的损伤中幸存下来， 但最终会屈服于一些次要事件。当能量储存在 在缺血灶中立即耗尽，在缺血灶周围 区域或半暗带(P)接近正常，尽管有显著积聚 乳酸盐。这种情况类似于弥漫性抑郁症，即 已知代谢成本很高，当然P已经处于危险之中 由于血流量低。病灶周围区域在24小时内发生梗塞 H和细胞死亡的机制只是一个推测问题。什么 很明显，P的死亡会导致长期的残疾 对局灶性中风的有效治疗仍然难以捉摸。 局灶性卒中患者代谢研究中遇到的问题 已经解决了。冰冻的大脑中的灶周和灶区 现在可以根据定量的血液来识别和解剖原位 流量值。马克杯组织中的代谢物可以很容易地测量出来 采用微量组织化学方法。将这两种方法结合起来 提供了一种独特的方法来研究代谢紊乱。 半影区。 这个应用程序的直接目标是确定不同的 这两个相邻区域的代谢反应是导致 P.神经递质、乳酸和钾的死亡被释放 在缺血期间，每一个都可以扩散到邻近的P区，创造一个 额外的工作量。对P的额外能源需求，其 血液流动受损，能量失衡加剧会导致 能量衰竭，细胞体积失去控制和脑梗塞。这 可能性将通过以下目标进行测试：1)在P中确定 和缺血核心能量代谢、酸碱平衡的变化， 大脑中动脉术后不同时间的水含量和神经递质代谢 闭塞，2)测量水肿形成的程度，直接在 解剖皮质组织或通过质子磁共振成像，并将这些变化关联起来 随着离散性解剖组织中电解质水平的变化 以及3)确定高血糖是否会降低phi和 增加缺血区的乳酸水平，将在 半暗带到a)要么加速发病，要么增加大小 梗塞和b)影响水肿的形成。其他针对以下目标的治疗 还将对可能的致病事件进行测试。 从这些实验中获得的信息将有助于为 开发一种中和缺血影响的干预措施 组织在邻近组织上，从而改善以下结果 通过最大限度地缩小梗塞范围来减少局部缺血。

The long-term goal of this project is to determine the role of tissue acid- base and metabolic derangements in the evolution of infarction following focal stroke. Experimental focal ischemia is more relevant to most human strokes than are global models. The information gained from focal models of ischemia, however, has been discouraging owing to the variability in the size and location of the lesion in existing models. Areas of reduced blood flow surrounding the ischemic focus following middle cerebral artery (MCA) occlusion apparently can survive the initial insult, but eventually succumb to some secondary event. While the energy stores are immediately depleted in the ischemic focus, those in the perifocal region or penumbra (P) are near normal despite a significant accumulation of lactate. This condition resembles that of spreading depression which is known to be metabolically costly, and certainly the P is already at risk owing to low blood flow. The perifocal region becomes infarcted within 24 H and the mechanisms of cell death are only a matter of speculation. What is clear is that the death of the P contributes to long-term disability and that effective treatment of focal stroke remain elusive. The problems encountered in the investigation of metabolism in focal stroke have been resolved. The perifocal and focal regions in brains frozen in situ now can be identified and dissected on the basis of quantitative blood flow values. Metabolites in mug pieces of tissue can be measured readily using microquantitative histochemistry. Combining these two methodologies provides an unique approach to study of the metabolic derangements in the penumbra. The immediate goal of this application is to determine if the disparate metabolic response of the two contiguous regions is the reason for the death of the P. Neurotransmitters, lactic acid and potassium are released during ischemia and each could diffuse to the adjacent P area, creating an additional work load. The additional energy demands on the P, its compromised blood flow, and an increasing energy imbalance would lead to energy failure, loss of cell volume control and infarction. This possibility will be tested by the following aims: 1) to determine in the P and ischemic core the changes in energy metabolism, acid-base balance, water content and neurotransmitter metabolism at various times after MCA occlusion, 2) to measure the extent of edema formation, either directly in dissected cortical tissues or by proton MRI, and to correlate these changes with alterations in electrolyte levels from discretely dissected tissues and 3) to determine if hyperglycemia, which is known to decrease pHi and increase lactate levels in ischemic areas, will act similarly in the penumbra to a) either hasten the onset of or increase the size of the infarct and b) affect edema formation. Other treatments targetted to putative pathogenic events will also be tested. The information gained from these experiments will help provide a basis for developing an intervention which will neutralize the influence of ischemic tissue on neighboring tissue and thereby improve the outcome following focal ischemia by minimizing the extent of the infarct.