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.

摘要 MRI已成为评估中风后脑损伤程度的标准方法 可能是指导治疗。该建议旨在：i)开发和实施新型的多参数磁共振成像 方法确定存活组织状态并观察疗效，ii)将这些方法应用于 氢化水、米诺环素及氢化水与米诺环素合用的疗效评价 在已建立的大鼠卒中模型中进行治疗。 第一部分涉及开发复杂的多模式磁共振成像采集和分析方法，以 纵向表征和跟踪组织活性、脑功能状态和脑血管反应性， 超过脑梗塞体积。第二部分涉及它们在研究氢水有效性方面的应用， 米诺环素、氢化水和米诺环素联合治疗。氢气或米诺环素 在实验性缺血性中风和其他疾病中，单独使用已被证明具有神经保护作用 神经紊乱。我们最近发现氢化水和米诺环素的结合显著 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 大鼠短暂(90min)大脑中动脉闭塞后。 我们的中心假设是氢水治疗可以减少梗塞面积、血管健康和 改善MRI检测的功能恢复，氢化水和米诺环素联合应用进一步 结果疗效显著。