Coordination Funds

在全球范围内，中风是导致成年人死亡的第二大原因，也是导致成年人长期残疾的主要原因。在德国，每两分钟就有一例新的中风病例。目前中风的治疗方案在很大程度上是有限的，有希望的实验结果往往无法在临床试验中得到验证。因此，迫切需要具有高转化潜力的基础脑卒中研究新途径，以成功开发有效的治疗策略。与此同时，缺血性脑损伤的炎症反应已被确定为促进脑卒中结局的关键病理机制。中风传统上不被认为是一种炎症性疾病，但它与（自身）免疫性脑疾病有许多共同特征。虽然这些神经炎症机制已经在缺血性脑损伤急性期得到了详细的描述，但脑卒中后慢性期恢复过程中脑免疫相互作用的机制仍有待澄清。同样，免疫调节干预对中风后修复和神经可塑性的影响几乎不为人所知。因此，本研究单元将重点研究神经炎症在中风后组织重塑和长期恢复中的作用。该联盟提出的项目旨在i)研究免疫细胞（尤其是小胶质细胞和T细胞）如何影响中风后的恢复过程；Ii)阐明神经炎症在脑卒中患者中的作用，并与小鼠系统进行比较；iii)确定中风后神经炎症的新生物标志物。最终，我们的研究联盟将解决有关未来卒中患者免疫调节试验的基本原理设计的关键问题，并将为实验性，多中心卒中研究建立新的标准。这些目标将在共同努力下实现，并通过使用尖端技术，包括功能和成像技术以及纳米体等新的治疗范例，以了解和调节中风后的免疫反应。我们的目标将通过来自基础免疫学、神经免疫学、中风免疫学和神经生物学领域的国际知名专家与该研究单位的临床中风研究人员的密切合作来实现。重要的是，所有临床前实验都将高度标准化，整个联合体将实施标准操作程序。这将允许一种全新程度的合作，我们将能够在研究项目和研究地点之间交换原始数据。关键发现将在第二阶段的多中心临床前随机对照试验（pRCT）中得到验证，我们的实验数据的转化相关性将通过对脑卒中患者的深入免疫、影像学和临床表型进行交叉验证。

On a global level stroke represents the second leading cause of death and the primary cause of long-term disability among adults. In Germany one new stroke occurs every two minutes. Current treatment options for stroke are largely limited, and promising experimental findings often fail validation in clinical trials. Hence, new avenues of basic stroke research with high translation potential are desperately needed in order to successfully develop effective treatment strategies. The inflammatory response to ischemic brain injury has meanwhile been well established as a key pathomechanism contributing to stroke outcome. Stroke is traditionally not considered an inflammatory disease, yet it shares multiple features with (auto)immune brain disorders. While these neuroinflammatory mechanisms have been described in great detail for the acute phase after ischemic brain injury, mechanisms of brain-immune interaction during recovery in the chronic phase after stroke still await clarification. Likewise, consequences of immunomodulatory interventions for post-stroke repair and neuroplasticity are barely understood. Therefore, this Research Unit will focus on studying the role of neuroinflammation for tissue remodeling and long-term recovery following stroke. The projects put forward by this consortium are designed to i) address how immune cells—particularly microglia and T cells—influence the recovery process following stroke; ii) clarify the role of neuroinflammation in stroke patients in comparison to the mouse system; and iii) identify novel biomarkers of post-stroke neuroinflammation. Ultimately, our research consortium will address key questions regarding the rationale design of future immunomodulatory trials in stroke patients and will establish new standards for experimental, multicenter stroke research. These goals will be achieved in a joint effort and by using cutting-edge technologies including functional and imaging technologies and new treatment paradigms such as nanobodies in order to understand and to modulate the immune responses after stroke. Our goals will be realized by the close collaboration of internationally recognized experts from the fields of basic immunology, neuroimmunology, stroke immunology, and neurobiology together with clinical stroke researchers within this Research Unit. Importantly, all preclinical experiments will be highly standardized and SOPs will be implemented for the entire consortium. This will allow a novel degree of collaboration in which we will be enabled to exchange raw data across research projects and study sites. Key findings will be validated in multicenter preclinical randomized controlled trials (pRCT) in the second funding phase, and the translational relevance of our experimental data will be cross-validated by in-depth immune, imaging and clinical phenotyping of stroke patients.