Metabolic Neuroprotection:Creatine Supplementation in Human Brain

描述（由申请人提供）：口服肌酸补充剂已被几个小组证明可以增加肌肉性能和质量。在大脑中也发现了高浓度的PCr和肌酸，其相对较高的耗氧量意味着，与肌肉相似，脑组织可能受到外源性肌酸的代谢影响。然而，虽然有大量的工作研究肌酸的使用如何影响肌肉的表现，但在大脑中可用的工作相对较少。在本提案中，我们将开始填补这一空白，在健康对照中进行高能磷酸盐、NAA、肌酸和灌注/氧化代谢的非侵入性MR测量。此外，由于越来越多的数据表明进行性代谢功能障碍可能直接导致癫痫的病理生理，我们还将研究口服肌酸补充剂对颞叶癫痫患者的代谢和临床影响。这项工作是与纽约大学综合癫痫中心的R. Kuzniecky医学博士合作完成的。特别是，癫痫已知对另一种形式的“代谢疗法”有反应，即高脂肪生酮饮食。正如我们之前使用磁共振光谱所显示的那样，生酮饮食的患者显示出大脑PCr/ATP的增加，而已知癫痫患者的大脑PCr/ATP减少。如果成功，该项目可能表明肌酸1)可以提供一种补充的治疗途径，2)为癫痫的代谢病理生理成分提供额外的证据。

DESCRIPTION (provided by applicant): Oral creatine supplementation has been demonstrated by several groups to increase muscle performance and mass. High concentrations of PCr and creatine are also found in the brain, which with its relatively high oxygen consumption means that, similar to muscle, brain tissue may be metabolically affected by exogenous creatine. However while there is extensive work examining how use of creatine affects muscle performance, there is relatively less work available in the brain. In this proposal we will begin to fill this gap, with non-invasive MR measurements of high energy phosphates, NAA, creatine and perfusion/oxidative metabolism in healthy controls. Furthermore, because of the increasing data that progressive metabolic dysfunction may contribute directly to the pathophysiology of epilepsy, we will also examine the metabolic and clinical effects of oral creatine supplementation in patients with temporal lobe epilepsy. This work is done in collaboration with R. Kuzniecky , MD with the NYU Comprehensive Epilepsy Center. In particular, epilepsy is known to respond to another form of "metabolic therapy", the high fat ketogenic diet. As we have previously shown using MR spectroscopy, patients placed on the ketogenic diet demonstrated increases in cerebral PCr/ATP, known to be decreased in epilepsy patients. If successful, this project may show that creatine 1) can provide a supplementary avenue of therapy and 2) contribute additional evidence for a metabolic pathophysiologic component to epilepsy.