Translational MR Imaging in Cocaine Pharmacotherapy Development

可卡因药物疗法开发中的转化磁共振成像

基本信息

批准号：
8004216
负责人：
PONNADA A NARAYANA
金额：
$ 32.99万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8004216
关键词：
Abstinence Adenosine Adenosine A2A Receptor Alzheimer&apos s Disease Amides Animal Model Animals Anisotropy Astrocytes Brain Carboxylic Acids Cerebrovascular Circulation Chemicals Chronic Cocaine Cocaine Abuse Cocaine Dependence Control Animal Controlled Environment Corpus Callosum Demyelinations Development Diffusion Magnetic Resonance Imaging Dopamine Dose Glutamates Grant Histologic Histology Human Huntington Disease Image Image Analysis Immunohistochemistry Individual Institutes Ischemic Brain Injury Laboratories Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Methods Monitor Myelin Names Nerve Degeneration Neurons Parkinson Disease Pathologic Pathology Pharmaceutical Preparations Pharmacotherapy Protons Radial Rattus Relative (related person)Resolution Rodent Spin Labels Structure Techniques Testing Therapeutic Tissues Translational Research Treatment Efficacy age related base brain tissue brain volume cerebral atrophy cocaine use effective therapy gray matter morphometry myelination neurofilament neuronal cell body neuropathology neuroprotection neurotoxic neurotoxicity normal aging novel piperidine receptor translational study white matter white matter change

项目摘要

Recent diffusion tensor imaging (DTI) studies fnsm our laboratory and others have demonstrated significantly reduced fractional anisotropy (FA) in the corpus callosum in cocaine-dependent subjects relative to controls. The changes in FA have been interpreted as an indication of altered myelin. The specific underlying neuropathology of these white matter changes and if these pathological changes can be altered by cocaine abstinence or novel phramacotherapy, however, remain to be determined. Understanding the pathological changes between nornial, healthy individuals and cocaine-addicts is not simple because of difficulties in creating a completely controlled environment. In addition, histologic confirmation of the proposed pathologic mechanism is difficult to realize in humans. In the proposed translational studies, using multi-modal magnetic resonance imaging and end point histology in rodents treated with chronic cocaine, we will determine the effects of 1) dose of cocaine and method of administration on a) regional brain atrophy measured on high resolution structural MRI with tensor based morphometry, b) white matter pathology as measured by DTI and magnetization transfer ratio, c) regional cerebral blood flow as determined by MRI-based arterial spin labeling, and d) metabolite concentrations as determined by proton magnetic resonance spectn^scopy and 2) administration of the novel adenosine A2A receptor antagonist SYN115 on cocaine associated white matter pathology, regional brain volumes and regional cerebral blood flow. These multi-modal studies in rodents should help characterize neuropathological changes and institute rational-based treatments in human cocaine abusers.

最近的扩散张量成像（DTI）研究FNSM我们的实验室和其他研究表明，相对于对照组，可卡因依赖性受试者的call体中的分数各向异性（FA）显着降低。 FA的变化被解释为髓磷脂改变的指示。这些白质变化的特定潜在神经病理学以及这些病理变化是否可以通过可卡因的戒酒或新颖的短语疗法改变，但仍有待确定。由于难以创建完全控制的环境，因此了解诺恩语，健康个体和可卡因瘾之间的病理变化并不简单。此外，在人类中难以实现对所提出的病理机制的组织学确认。 In the proposed translational studies, using multi-modal magnetic resonance imaging and end point histology in rodents treated with chronic cocaine, we will determine the effects of 1) dose of cocaine and method of administration on a) regional brain atrophy measured on high resolution structural MRI with tensor based morphometry, b) white matter pathology as measured by DTI and magnetization transfer ratio, c) regional cerebral blood flow as由基于MRI的动脉自旋标记确定，D）由质子磁共振光谱和2）在可卡因相关的白质病理学，区域脑容量和区域大脑血流上确定的新型腺苷A2A受体拮抗剂Syn115确定的代谢产物浓度。这些在啮齿动物中的多模式研究应有助于表征神经病理学的变化，并在人类可卡因滥用者中提出基于理性的治疗方法。