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

该项目为NINDS项目卒中前评估网络(SPAN)在耶鲁大学建立了一个小鼠临床前治疗试验点，以支持急性神经保护的转化性研究。一个由研究中风后神经血管损伤机制的基础科学家、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组成的研究团队正在组建一个高度协作和互动的团队，致力于在国家协调中心的监督下测试NINDS选择的候选神经保护剂。总的目标是确定最有希望的新中风疗法的候选者，然后在临床试验中进行测试，促进中风患者的护理。该团队建议将Fingolimod作为一种潜在的缺血性中风治疗方法，并在该网络中进行测试。在目的1中，将测试再灌流时口服Fingolimod对青年和老年小鼠在使用和不使用组织纤溶酶原激活剂(TPA)的情况下脑梗塞范围和神经行为结果的影响。在目标2中，将测试口服Fingolimod在有和没有tPA的男女高血糖/糖尿病环境下对中风结果的影响。目的3测试口服液在重叠感染环境中的有效性和安全性。这些目的将从临床相关的生物学变量、合并症和治疗方面评估Fingolimod在改善小鼠脑缺血模型卒中结果方面的有效性。

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.