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 已成为评估中风后大脑损伤程度的标准方法 可能指导治疗。该提案旨在： i) 开发和实施新型多参数 MRI 确定活力组织状态并研究治疗效果的方法，ii) 将这些方法应用于 评估氢水、米诺环素以及氢水和米诺环素组合的功效 在已建立的大鼠脑卒中模型中进行治疗。 第一部分涉及开发复杂的多模态 MRI 采集和分析方法，以 纵向表征和跟踪组织活力、脑功能状态和脑血管反应性， 超出梗塞体积。第二部分涉及它们在研究氢水功效方面的应用， 米诺环素，以及氢水和米诺环素联合治疗。氢气或米诺环素 单独已被证明对实验性缺血性中风以及其他疾病具有神经保护作用 神经系统疾病。我们最近发现氢水和米诺环素的组合显着 减少 MRI 定义的病变体积、灰质细胞毒性、白质损伤和行为缺陷 短暂（90 分钟）大脑中动脉闭塞后的大鼠。 我们的中心假设是氢水治疗可减少梗塞面积、血管健康和 MRI 检测发现，氢水和米诺环素的组合可改善功能恢复 从而达到卓越的功效。