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中心，以支持急性神经保护的转化研究。一组研究人员，包括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管理员，正在形成一个高度协作和互动的团队，致力于测试NINDS选择的候选神经保护剂在国家协调中心的监督下。总体目标是确定最有前途的候选人，然后在临床试验中进行测试，推进中风患者的护理。该团队提出芬戈莫德作为缺血性中风的潜在治疗方法在网络中进行测试。在目的1中，将测试在再灌注时施用的口服芬戈莫德对具有和不具有组织纤溶酶原激活物（tPA）的两种性别的年轻和老年小鼠中的梗塞大小和神经行为结果的有效性。在目标2中，将测试口服芬戈莫德在有和没有tPA的两种性别的高血糖症/糖尿病的情况下对中风结局的影响。目的3验证口服芬戈莫德治疗合并感染的有效性和安全性。这些目的将共同评价芬戈莫德在临床相关生物学变量、合并症和治疗的背景下改善脑缺血小鼠模型中卒中结局的疗效。

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.