ENERGY METABOLISM

能量代谢

基本信息

批准号：
6318356
负责人：
MICHAEL B SMITH
金额：
$ 15.82万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-01 至 2001-06-30
项目状态：
已结题

项目摘要

The overall objective of this research component is to investigate the high-energy biochemical mechanisms whereby the perinatal brain is damaged by hypoxia-ischemia and how brain injury can be prevented or reduced through specific modalities of therapy. Specific Aims include: 1) to characterize the earliest alterations in high-energy phosphate reserves which occur during perinatal cerebral hypoxia-ischemia and to correlate these changes with perturbations in cerebral energy utilization, cerebral glucose utilization, glutamate and nitric oxide neurotoxicity, and intracellular calcium accumulation; 2) to correlate the concentrations in cerebral high-energy phosphate reserves and the changes which occur during hypoxia-ischemia using 31P magnetic resonance (MR) spectroscopic methods and enzymatic, fluorometric techniques; 3) to characterize the secondary (delayed) energy failure which occurs during recovery from perinatal cerebral hypoxia-ischemia and to correlate the alterations with the presence and severity of hypoxia-ischemic brain damage; 4) to ascertain underlying biochemical mechanisms whereby the glucocorticosteroid, dexamethasone, protects the perinatal brain from hypoxic-ischemic damage; 5) to determine the protective influence of magnesium sulfate on perinatal hypoxic-ischemic brain damage and, if so, to ascertain its mechanism of action; and 6) to investigate further the presence and extend of alterations in diffusion-weighted and T2-weighted imaging during recovery from perinatal cerebral hypoxia-ischemia and to correlate any changes with the nature and extent of cerebral edema and associated neuropathologic alterations. Seven-days postnatal rats will undergo unilateral cerebral hypoxia-ischemia, during and following which the animals will undergo those procedures necessary to obtain sequential 31P and 1H NMR spectra which will allow for measurements of the alterations in high-energy phosphate reserves and other metabolites which result from the insult. Other animals will undergo MR imaging at specific intervals following cerebral hypoxia-ischemia. Other experiments will elucidate the neuroprotective effect of dexamethasone, magnesium sulfate, and L-NAME on hypoxic-ischemic brain damage in the developing rat. Analytic procedures will include sequential measures with NMR spectroscopy as well as brain tissue analysis of high-energy phosphate reserves and other metabolites using enzymatic, fluorometric techniques.

该研究成分的总体目的是研究高能生化机制，从而通过缺氧 - 缺血症损害了围产期大脑，以及如何通过特定的治疗方式来预防或减少脑损伤。具体目的包括：1）表征在围产期大脑缺氧 - 缺血期间发生的高能磷酸盐储量的最早变化，并将这些变化与脑能量利用率的扰动相关，脑葡萄糖利用率，谷氨酸和硝酸氧化物氧化物神经毒性和肠内钙化; 2）使用31p磁共振（MR）光谱方法和酶促，荧光计量学技术，将脑高能磷酸盐储量的浓度以及在缺氧 - 缺血期间发生的变化相关联； 3）表征从围产期脑缺氧 - 缺血性恢复期间发生的次级（延迟）能量故障，并将改变与缺氧 - 缺血性脑损伤的存在和严重程度相关联； 4）确定基本的生化机制，糖皮质激素（地塞米松）可以保护围产期大脑免受低氧 - 缺血性损害的影响； 5）确定硫酸镁对围产期缺氧 - 缺血性脑损伤的保护性影响，并确定其作用机理； 6）为了进一步研究从围产期脑脑缺氧 - 缺血血症恢复过程中扩散加权和T2加权成像的改变和扩展，并将任何变化与脑水肿的性质和程度相关联和相关的神经病理学改变。七天后大鼠将经历单侧脑缺氧 - 缺血性，在此期间和随后，动物将经历那些获得顺序的31p和1H NMR光谱所需的程序，这将允许测量高能磷酸盐储量和其他由枪支产生的高能磷酸盐储量和其他代谢物的变化。其他动物将在脑缺氧 - 缺血性脑部后以特定的间隔进行MR成像。其他实验将阐明地塞米松，硫酸镁和L-名称对发育中大鼠缺氧 - 缺血性脑损伤的神经保护作用。分析程序将包括使用NMR光谱法以及使用酶促的荧光技术对高能磷酸盐储量和其他代谢产物进行脑组织分析的顺序测量。