MRI Study of Hydrogen Water and Minocycline Combination Therapy for Ischemic Stroke

氢水与米诺环素联合治疗缺血性中风的MRI研究

• 批准号: 10564735
• 负责人: Timothy Q. Duong
• 金额: $ 42.64万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10564735
• 关键词: Acute; Address; Alteplase; Ambulances; Anatomy; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Autophagocytosis; Behavioral; Blood Vessels; Brain; Brain Ischemia; Cause of Death; Cell-Mediated Cytolysis; Cerebrum; Characteristics; Chronic Phase; Classification; Clinical Trials; Combined Modality Therapy; Data; Development; Diffusion; Dose; Double-Blind Method; Evolution; Experimental Designs; FDA approved; Failure; Free Radicals; Health; Histologic; Histology; Hour; Human; Hydrogen; Individual; Infarction; Inflammation; Injury; Ischemia; Ischemic Stroke; Lesion; Magnetic Resonance Imaging; Measures; Metabolic; Methods; Middle Cerebral Artery Occlusion; Minocycline; Modeling; Multiple Trauma; Neurologic; Operative Surgical Procedures; Pathway interactions; Perfusion; Phase; Physiological; Quality of life; Randomized; Rattus; Recovery of Function; Reperfusion Therapy; Risk; Safety; Stroke; Therapeutic Effect; Thrombolytic Therapy; Time; Tissue Viability; Tissues; Treatment outcome; Water; Work; acute stroke; behavior test; behavioral outcome; cerebrovascular; chronic stroke; clinical decision-making; comparative efficacy; cytotoxicity; disability; dosage; effective therapy; efficacy evaluation; functional status; gray matter; improved; in vivo; innovation; ischemic injury; molecular hydrogen; multimodality; nervous system disorder; neuroprotection; novel; novel therapeutic intervention; post stroke; prevent; response; spatiotemporal; stroke clinical trials; stroke model; stroke patient; stroke therapy; water treatment; white matter; white matter damage

ABSTRACT MRI has become a standard method to evaluate the extend of injury in the brain after stroke and possibly guide treatments. This proposal aims to: i) develop and implement novel multiparametric MRI methods to determine viability tissue status and to investigate therapeutic effects, ii) to apply these methods to evaluate the efficacy for hydrogen water, minocycline, and combination of hydrogen water and minocycline treatment in the established rat stroke model. Part one involves development of sophisticated multimodal MRI acquisition and analysis methods to longitudinally characterize and track tissue viability, cerebral functional status, and cerebral vascular reactivity, beyond infarct volume. Part two involves their applications to investigate the efficacy for hydrogen water, minocycline, and combination of hydrogen water and minocycline treatment. Hydrogen or minocycline individually has been shown to be neuroprotective in experimental ischemic stroke as well as other neurological disorders. We recently found that the combination of hydrogen water and minocycline markedly reduces MRI-defined lesion volume, gray-matter cytotoxicity, white-matter damage, and behavioral deficits in rats after transient (90-min) middle cerebral artery occlusion. Our central hypothesis is that hydrogen water treatment reduces infarct size, vascular health, and improves functional recovery as detected by MRI, and the combined hydrogen water and minocycline further results in superior efficacy.

抽象的 MRI已成为评估中风后脑部损伤延伸的标准方法和 可能指导治疗。该建议的目的是：i）开发和实施新颖的多参数MRI 确定可行性组织状态和研究治疗作用的方法，ii）将这些方法应用于 评估氢水，米诺环素和氢水和米诺环素的组合的疗效 在已建立的大鼠中风模型中的处理。 第一部分涉及开发复杂的多模式MRI获取和分析方法 纵向表征和跟踪组织生存力，脑功能状态和脑血管反应性， 超出梗塞量。第二部分涉及他们的应用来研究氢水的功效， 牛油水和米诺环素治疗的组合。氢或米诺环素 已显示在实验性缺血性中风以及其他方面具有神经保护作用 神经系统疾病。我们最近发现，氢水和米诺环素的结合显着 减少MRI定义的病变体积，灰色 - 物质细胞毒性，白色损伤和行为缺陷 瞬时（90分钟）中大脑动脉阻塞后的大鼠。 我们的中心假设是氢水处理可降低梗塞大小，血管健康和 改善MRI检测到的功能恢复，并进一步进一步 产生卓越的功效。