Measuring in Vivo Meth-induced Neurovascular Changes Using Quantitative MRI

使用定量 MRI 测量体内冰毒引起的神经血管变化

• 批准号: 8426291
• 负责人: Carmela M Reichel
• 金额: $ 22.13万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8426291
• 关键词: Abstinence; Acute; Address; Animal Model; Area; Astrocytes; Attentional deficit; Behavioral; Blood - brain barrier anatomy; Blood Vessels; Blood flow; Cerebrovascular Circulation; Cerebrum; Chronic; Cognitive deficits; Consumption; Corpus striatum structure; Coupling; Data; Diagnostic; Diffusion Magnetic Resonance Imaging; Dose; Edema; Encephalitis; Endothelial Cells; Exposure to; Family; Health; High Prevalence; Homeostasis; Human; Image; Imaging Techniques; Impairment; Inflammation; Inflammatory; Inflammatory Response; Knowledge; Long-Term Effects; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Matrix Metalloproteinases; Measures; Methamphetamine; Methamphetamine dependence; Modeling; Neurons; Outcome; Pattern; Permeability; Pharmaceutical Preparations; Predisposition; Property; Proteins; Rattus; Recording of previous events; Regimen; Relapse; Research; Rodent Model; Saline; Self Administration; Self-Administered; Societies; Spin Labels; Techniques; Testing; Tight Junctions; Time; Tissues; Treatment outcome; Unit of Measure; Vascular System; Withdrawal; addiction; base; clinically relevant; design; experience; improved; in vivo; inflammatory marker; interest; male; methamphetamine abuse; methamphetamine exposure; neuroadaptation; neuroimaging; neuroinflammation; neurotoxicity; neurovascular unit; novel; public health relevance; relating to nervous system; research study; response; success; treatment planning; white matter; white matter damage

DESCRIPTION (provided by applicant): An estimated 26 million people abuse methamphetamine (meth) worldwide. This high prevalence of abuse and the ensuing health and societal consequences necessitates a clear need to understand the long-term neural and vascular adaptations caused by chronic meth that contribute to addiction and relapse. Meth exposure interferes with the neuronal and vascular function required to establish connectivity and wiring of interconnected networks. An integral part of vascular-neural coupling, the blood brain barrier (BBB), is particularly sensitive to inflammatory mechanisms and BBB health reflects the general health of neurovascular crosstalk. Acute exposure to high doses of meth results in neuroinflammation and subsequent increases in BBB permeability. However, the long-term consequence of chronic meth-induced neuroinflammation on neurovascular health is an understudied area of meth addiction. Notably, these issues have not been addressed using a clinically relevant rodent model of meth addiction. Our central hypothesis is that chronic self-administered meth results in lasting neuroinflammation that compromises neural-vascular coupling of the BBB. To test this hypothesis, we will use cutting edge magnetic resonance based neuroimaging techniques to identify the progression of inflammation following prolonged meth self-administration. These inflammatory responses may be early indicators for meth-induced damage to neurovascular units and subsequent break down of the BBB. We will measure the time course of meth-induced changes in neuronal and vascular integrity during abstinence from meth by measuring white matter integrity and BBB transfer rate to map progressive tissue damage. These assessments are not possible by relying solely on histological outcomes. Therefore, the end point results will be correlated with histological outcomes on endothelial and inflammatory markers. The imaging experiment is designed to acquire information about spatial and temporal patterns of damage to neurovascular unit providing valuable information on the progression of meth-induced adaptations. Further, this study will provide novel information for diagnostic and treatment planning for meth addiction.

描述（由申请人提供）：估计全世界有 2600 万人滥用甲基苯丙胺 (meth)。滥用现象的高发以及随之而来的健康和社会后果，明确需要了解慢性冰毒引起的长期神经和血管适应，从而导致成瘾和复发。冰毒暴露会干扰建立互连网络的连接和布线所需的神经元和血管功能。血脑屏障（BBB）是血管-神经耦合的一个组成部分，对炎症机制特别敏感，BBB 的健康状况反映了神经血管串扰的总体健康状况。急性接触高剂量的冰毒会导致神经炎症，并随后导致血脑屏障通透性增加。然而，慢性冰毒引起的神经炎症对神经血管健康的长期影响是冰毒成瘾的一个尚未得到充分研究的领域。值得注意的是，这些问题尚未通过临床相关的冰毒成瘾啮齿动物模型得到解决。我们的中心假设是，长期自行服用冰毒会导致持久的神经炎症，从而损害血脑屏障的神经血管耦合。为了检验这一假设，我们将使用基于磁共振的尖端神经影像技术来识别长期自我服用冰毒后炎症的进展。这些炎症反应可能是冰毒引起的神经血管单位损伤和随后血脑屏障破坏的早期指标。我们将通过测量白质完整性和血脑屏障转移率来绘制渐进性组织损伤图，从而测量戒除冰毒期间冰毒引起的神经元和血管完整性变化的时间过程。仅依靠组织学结果无法进行这些评估。因此，终点结果将与内皮和炎症标志物的组织学结果相关。成像实验旨在获取有关神经血管单元损伤的空间和时间模式的信息，从而提供有关冰毒诱导的适应进展的有价值的信息。此外，这项研究将为冰毒成瘾的诊断和治疗计划提供新的信息。