In vivo measures of mitochondrial function in epilepsy

癫痫线粒体功能的体内测量

• 批准号: 6495437
• 负责人: Hoby P Hetherington
• 金额: $ 22.55万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6495437
• 关键词: Krebs' cycle; bioenergetics; bioimaging /biomedical imaging; brain metabolism; clinical research; glucose metabolism; high energy compound; human subject; mitochondria; neurochemistry; nuclear magnetic resonance spectroscopy; partial seizure; positron emission tomography; temporal lobe /cortex disorder

Epilepsy is one of the most common neurological disorders, affecting one to two million Americans. For approximately 10% of these individuals, the debilitating effects of the disease can not be controlled by medication. Although surgical intervention is highly effective, accurate lateralization and localization of seizure foci based on metabolic measurements have been developed. These techniques include measures of CMRglucose by FDG PET, high-energy phosphates (PCr and ATP) by 31 NMR and measurements of neuronal dysfunction with 1H NMR measurements of N-acetyl aspartate. Although these methodologies have been quite successful (sensitivity and specificity of 70-95%) in the lateralization of mesial temporal lobe epilepsy, the biological mechanisms underlying these observations remains controversial. The findings of decreased high- energy phosphates along with decreased CMRglucose suggest that energy production is impaired. Furthermore, the finding that NAA reductions are 1) reversible and 2) not solely due to neuronal loss; in conjunction with 3) results in mitochondrial preparations linking NAA synthesis rates, ATP production and inhibition of mitochondrial enzymes suggest that the metabolic defect may be due to impaired mitochondrial function. Therefore, the goal of this project is to investigate the role of impaired mitochondrial function. Therefore, the goal of this project is to investigate the role of impaired mitochondrial function as a primary cause for the observed metabolic alterations in temporal lobe epilepsy. To achieve this goal we will combine in vivo measurements of high energy phosphates, NAA, glutamate and TC cycle rate (NMR) and CMRglucose (PET) from patients with temporal lobe epilepsy with detailed measurements of anapleurosis, neurotransmitter cycling (Project 2), mitochondrial function (Project 3) from the resected tissue and the corresponding functional changes in ion homeostasis (Project 4).

癫痫是最常见的神经系统疾病之一，影响了1-200万美国人。对于这些人中，大约有10％的人无法通过药物控制该疾病的衰弱作用。尽管手术干预非常有效，但已经开发了基于代谢测量值的癫痫发作焦点的准确侧向化和定位。这些技术包括通过FDG PET，高能磷酸盐（PCR和ATP）通过31 NMR测量CMRGlucose的测量，以及通过N-乙酰基甲甲酸酯的1H NMR测量值测量神经元功能障碍。尽管这些方法在中颞叶癫痫的横向化中取得了很大成功（敏感性和特异性为70-95％），但这些观察结果的生物学机制仍然有争议。高能磷酸盐降低以及CMRGLUCOSE降低的发现表明能量产生受到损害。此外，NAA减少是1）可逆的发现，而不是仅仅是由于神经元丧失而引起的；结合3）导致线粒体制剂连接NaA合成速率，ATP产生和对线粒体酶的抑制，这表明代谢缺陷可能是由于线粒体功能受损所致。因此，该项目的目的是研究线粒体功能受损的作用。因此，该项目的目的是研究线粒体功能受损的作用，这是观察到的颞叶癫痫发生的代谢改变的主要原因。为了实现这一目标，我们将结合颞叶癫痫患者的高能磷酸盐，NAA，谷氨酸和TC循环速率（NMR）（NMR）和Cmrglucose（NMR）（PET），以及对无足质尿液的详细测量，对无足质释放，神经释放剂（项目2），MITOCHORIAL官方官方（MITOCHORIAIL官能组织）的详细测量。稳态（项目4）。