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

摘要 MRI已成为评价脑卒中后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 确定存活组织状态和研究治疗效果的方法，ii）将这些方法应用于 评价氢水、米诺环素以及氢水和米诺环素联合用药的疗效 在建立的大鼠中风模型中的治疗。 第一部分涉及复杂的多模态MRI采集和分析方法的开发， 纵向表征和跟踪组织活力、脑功能状态和脑血管反应性， 超出梗死体积。第二部分是它们在氢水效能研究中的应用， 二甲胺四环素，以及氢水和二甲胺四环素治疗的组合。氢或米诺环素 在实验性缺血性中风以及其它中风中， 神经系统疾病我们最近发现，氢水和米诺环素的组合明显 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，氢水治疗可以减少梗死面积，血管健康， 通过MRI检测改善了功能恢复，并且组合的氢水和米诺环素进一步 导致上级功效。

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.