Stroke Preclicinal Assessment Network

关于潜在卒中治疗的探索性动物数据尚未预测临床成功。那里 关注临床前研究的设计和实施，其可重复性和可推广性。的 NINDS卒中临床前评估网络（SPAN）对这一挑战做出了回应， 多中心平台，用于转化性卒中研究中的临床前确证性研究。MGH团队 在同行评审为第一次迭代的SPAN（SPAN-1）选择的六个实验室中。 我们对SPAN-1的设计做出了重大贡献。MGH负责MRI方案， SPAN-1，并帮助开发了一个全自动的分析管道。然后，我们贡献了近400只动物， 在2年内测试六种不同的急性中风干预措施。每只动物接受两次MRI（第2天和第30天） 以及两次神经学测试（第7天和第28天）。在28天生存期内，总死亡率仅为~10%。我们 技术损失仅为17头动物。仅有3例方案偏离或违背。我们 总体目标是在SPAN的下一次迭代（SPAN-2）中重复这一成功。 我们是一个经验丰富的临床和基础科学家团队，能够适应 网络MGH SPAN团队已经集体发表了100多篇使用各种局灶性脑损伤的手稿， 缺血模型和急性和慢性神经学结果读数。MGH还将带来 SPAN-2的其他创新方法，例如引入MRI读数， 转化、血脑屏障（BBB）破坏和纤维束成像。我们将补充后者， 随访期结束时静息状态功能连接（RSFC）的光学成像。 目标1.作为测试实验室为SPAN-2做出贡献。我们保证在SPAN-1中重复我们的成功， 作为一个团队与网络的其他部分合作，并通过内置的冗余来维持我们的高标准， 确保我们在面对人事变动以及流行病和天气等破坏性事件时的应变能力。 目标2.引入创新的新结构和功能指数，以丰富SPAN读数。我们将 通过引入创新的读数，如出血，水肿， 结构和功能连接，以及组织学分析，这些都不是SPAN-1的一部分。 目标3。测试无偏倚、多中心、随机和盲态临床前试验网络是否可以 证实或反驳已发表的探索性疗效和安全性数据。我们假设SPAN将拥有 统计能力和公正的结构，以提供确凿的证据，证实或反驳发表 缺血性中风联合再灌注的前瞻性脑保护疗法的探索性数据。 十多年来，我们一直倡导并热情支持公正的概念， 多中心临床前试验平台。我们热情地作为SPAN-1的一部分工作，以确保其成功。 现在，我们完全致力于支持SPAN-2，使其取得成功。

Exploratory animal data on potential stroke therapies has not been predictive of clinical success. There are concerns over the design and conduct of pre-clinical studies, their reproducibility and generalizability. The response to this challenge was the NINDS Stroke Preclinical Assessment Network (SPAN), an unbiased multicenter platform for preclinical confirmatory studies in translational stroke research. The MGH team was among the six laboratories selected by the peer review for this first iteration of SPAN (SPAN-1). We made major contributions to the design of SPAN-1. MGH took charge of the MRI protocol for SPAN-1 and helped develop a fully automated analysis pipeline. We then contributed almost 400 animals in under 2 years to test six different acute stroke interventions. Each animal underwent two MRIs (days 2 and 30) and two neurological tests (days 7 and 28). Overall mortality was only ~10% during 28-day survival. Our technical losses amounted to just 17 animals. There were only 3 protocol deviations or violations. Our overarching aim is to repeat this success in the next iteration of SPAN (SPAN-2). We are an experienced team of clinical and basic scientists capable of adjusting to the needs of the network. MGH SPAN team has collectively published over 100 manuscripts using various focal cerebral ischemia models and acute and chronic neurological outcome readouts in rodents. MGH will also bring additional innovative approaches to SPAN-2, such as introducing MRI readouts for hemorrhagic transformation, blood-brain barrier (BBB) disruption and tractography. We will complement the latter with optical imaging of resting state functional connectivity (RSFC) at the end of the follow up period. Aim 1. Contribute to SPAN-2 as a testing laboratory. We pledge to repeat our success in SPAN-1, working as a team with the rest of the network and sustaining our high standards with built-in redundancies to ensure our resilience in the face of personnel changes and disruptive events such as pandemics and weather. Aim 2. Introduce innovative new structural and functional indices to enrich the SPAN readouts. We will go beyond recruiting subjects for the trial by introducing innovative readouts such as hemorrhage, edema, structural and functional connectivity, and histological analyses, which have not been part of SPAN-1. Aim 3. Test whether an unbiased, multicenter, randomized, and blinded preclinical trial network can confirm or refute the published exploratory efficacy and safety data. We hypothesize that SPAN will have the statistical power and an unbiased structure to provide conclusive evidence confirming or refuting published exploratory data of prospective cerebroprotective therapies in ischemic stroke in combination with reperfusion. For over a decade, we have advocated for and passionately supported the concept of an unbiased multicenter preclinical testing platform. We enthusiastically worked as part of SPAN-1 to ensure its success. And now we are fully committed to support SPAN-2 to make it a success as well.