Yale site for Stroke Preclinical Assessment Network (SPAN) for Acute Neuroprotection

耶鲁大学中风临床前评估网络 (SPAN) 急性神经保护网站

基本信息

批准号：
10216372
负责人：
LAUREN H SANSING
金额：
$ 53.62万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10216372
关键词：
Acute Aging Alteplase Antibacterial Response Biological Brain Caring Cell Death Cerebral Edema Cerebral Ischemia Clinical Clinical Research Clinical Trials Collaborations Data Diabetes Mellitus Disease Effectiveness Ensure Event FDA approved Failure Female Goals Hemorrhage Heterogeneity Human Hyperglycemia Hyperglycemic Mice Immune response Immunomodulators Impairment Individual Infarction Infection Inflammation Inflammatory Inflammatory Response Injury Ischemia Ischemic Stroke Leukocytes Methodology Microglia Middle Cerebral Artery Occlusion Modeling Morbidity - disease rate Multiple Sclerosis Mus National Institute of Neurological Disorders and Stroke Neurologic Neurons Neuroprotective Agents Oligodendroglia Oral Outcome Pathway interactions Patients Perfusion Pharmaceutical Preparations Physicians Pneumonia Preclinical Testing Recovery of Function Reperfusion Therapy Reporting Research Design Research Personnel Risk Rodent Safety Scientist Site Specialist Stroke Testing Therapeutic Intervention Thrombectomy Translations Work acute stroke aged analog bioimaging clinically relevant comorbidity data sharing diabetic disability effectiveness evaluation efficacy evaluation efficacy testing improved improved outcome interest lipophilicity male mortality mouse model multiple sclerosis treatment neurobehavioral neuroprotection neurovascular injury novel oxidative damage post stroke pre-clinical pre-clinical assessment pre-clinical research prevent programs recruit safety testing sex sphingosine 1-phosphate stroke model stroke outcome stroke patient stroke risk stroke therapy targeted treatment therapeutic candidate therapeutic evaluation thromboinflammation tissue injury translational scientist translational study

项目摘要

The project establishes a murine preclinical stroke therapeutics testing site at Yale for the NINDS program Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies for Acute Neuroprotection. A team of investigators including basic scientists studying mechanisms of neurovascular injury after stroke, translational researchers, biomedical imaging specialists, clinical trialists, acute stroke clinicians, and a data manager are forming a highly collaborative and interactive team dedicated to testing candidate neuroprotectants selected by NINDS under the oversight of a national coordinating center. The overall goal is to identify the most promising candidates for novel stroke therapies to then be tested in clinical trials, advancing the care for stroke patients. The team proposes fingolimod as a potential therapy for ischemic stroke to be tested in the network. In Aim 1, the effectiveness of oral fingolimod administered at reperfusion on infarct size and neurobehavioral outcomes in young and aged mice of both sexes with and without tissue plasminogen activator (tPA) will be tested. In Aim 2, the effects of oral fingolimod on stroke outcomes in the setting of hyperglycemia/ diabetes in both sexes with and without tPA will be tested. Aim 3 will test the efficacy and safety of oral fingolimod in the setting of coincident infection. Together these Aims will evaluate the efficacy of fingolimod in improving stroke outcomes in murine models of cerebral ischemia in the setting of clinically-relevant biological variables, comorbidities, and treatments.

该项目在耶鲁大学为Ninds计划中风临床前评估网络（SPAN）建立了一个鼠临床前中风治疗现场，以支持急性神经保护的翻译研究。一个研究人员团队，包括基础科学家研究中风后神经血管损伤的机制，翻译研究人员，生物医学成像专家，临床试验人员，急性中风临床医生和数据经理正在组建一个高度协作和互动的团队，致力于测试由NINDS下的Ninds Orcontighting Anterighting Anterighting Comportation Cermortination Center中心进行测试的候选候选人。总体目标是确定在临床试验中测试新型中风疗法的最有希望的候选者，从而推进了中风患者的护理。该团队建议在网络中测试缺血性中风的潜在疗法。在AIM 1中，将测试两性男性和没有组织纤溶酶激活剂（TPA）的年轻小鼠和老年小鼠的梗死大小和神经行为结局时口服芬诺氏菌的有效性。在AIM 2中，将测试口服fingolimod对中风结果的影响，在两性具有和没有TPA的性别的高血糖/糖尿病的情况下。 AIM 3将测试口服芬洛莫德在一致感染的情况下的功效和安全性。这些目的共同评估芬诺莫德在临床上与临床相关的生物学变量，合并症和治疗方面的鼠模型中改善中风结果的疗效。