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

该项目在耶鲁大学为NINDS中风临床前评估网络（SPAN）项目建立了一个小鼠临床前中风治疗试验点，以支持急性神经保护的转化研究。一组研究人员包括研究脑卒中后神经血管损伤机制的基础科学家、转化研究人员、生物医学成像专家、临床试验学家、急性中风临床医生和一名数据管理人员，他们组成了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。总体目标是确定最有希望的新型中风治疗候选药物，然后在临床试验中进行测试，推进对中风患者的护理。该团队提出芬戈莫德作为缺血性中风的潜在治疗方法，将在网络中进行测试。在Aim 1中，将测试在再灌注时口服fingolimod对年轻和老年小鼠（无论有无组织纤溶酶原激活剂（tPA））的梗死面积和神经行为结果的有效性。在Aim 2中，将测试口服芬戈莫德对男女高血糖/糖尿病患者卒中结局的影响，无论是否使用tPA。目的3将测试口服芬戈莫德在合并感染情况下的疗效和安全性。综上所述，这些目的将在临床相关生物学变量、合并症和治疗的背景下评估芬戈莫德在改善脑缺血小鼠模型脑卒中结局方面的疗效。

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.