INVESTIGATION OF CHRONIC POST ISCHEMIC BRAIN ALKALOSIS

描述(改编自申请人的摘要)：具体目的 本研究旨在阐明脑缺血后与脑损伤的关系 组织碱中毒和缺血性神经元损伤，最终导致 证明核磁共振测量的脑碱中毒是一个有用的标记物 神经元损伤。以下具体目标与这一目标是一致的： 1)用活体~(31)P磷核磁共振波谱测量脑的pH值 在诱导缺血后连续一周，并还 测量同一组织中的神经元损伤。这些测量结果将是 作为短暂性前脑缺血持续时间的函数，AS 以及对大鼠进行“保护性”低温干预。这个 正在测试的假设是神经细胞损伤的程度是 与疾病的大小、发病时间和持续时间直接相关 从相同的组织中检测到碱中毒。这种关联的基础是 碱中毒的时间分布反映了细胞炎症 突起，与神经元损伤有关。2)测量，特别是 缺血后的时间点、炎性细胞反应和胶质细胞 增殖、神经元损伤和脑组织pH值，作为 短暂性前脑缺血持续时间和体温过低 干预。正在测试的假设是炎性细胞 反应和胶质细胞增殖与神经元损伤直接相关； 因此，脑组织碱中毒与神经元损伤直接相关。3) 结合上述研究测量脑血流量和 脑部高能磷酸盐和乳酸盐的相对浓度。 这些测量将解决脑组织之间的关系 碱中毒，以及脑血流量和组织代谢的变化。 提示脑缺血后pH的变化将是密切耦合的。 最终的组织存活能力，因此研究将强调 慢性pH值测定对卒中的潜在诊断意义 病人。

DESCRIPTION (Adapted from the applicant's abstract): The specific aim of this study is to clarify the relationship between post ischemic brain tissue alkalosis and ischemic neuronal damage, and ultimately to demonstrate that brain alkalosis, as measured by NMR, is a useful marker of neuronal injury. The following Specific Aims are in accord with this goal: 1) To measure brain pH, using in vivo 31P phosphorous NMR spectroscopy serially for one week following the induction of ischemia, and to also measure neuronal damage in the same tissue. These measurements will be performed as a function of the duration of transient forebrain ischemia, as well as for a "protective" hypothermic intervention in the rat. The hypothesis being tested is that the extent of neuronal cell damage is directly correlated with the magnitude, onset time and duration of alkalosis detected from the same tissue. The basis for this correlation is that the temporal profile of alkalosis reflects cellular inflammatory processes, associated with neuronal damage. 2) To measure, at particular time points after ischemia, inflammatory cellular response and glial proliferation, neuronal damage and brain tissue pH, as a function of the duration of transient forebrain ischemia and for a hypothermic intervention. The hypothesis being tested is that inflammatory cellular response and glial proliferation is directly correlated to neuronal damage; hence brain tissue alkalosis is directly correlated to neuronal damage. 3) To measure, in conjunction with the above studies, cerebral blood flow and relative concentrations of brain high energy phosphates and lactates. These measurements will address the relationship between brain tissue alkalosis, and CBF and metabolic changes in the tissue. It is proposed that post ischemic brain pH changes will be closely coupled to ultimate tissue viability, and that the studies will therefore highlight the potential diagnostic significance of chronic pH measurements in stroke patients.