Blocking and modulation of Spreading Depolarisations in a gyrencephalic brain under high-definition multimodal monitoring including novel multispectral optical and photoacoustic tissue analysis

在高清多模态监测下阻断和调节环脑的扩散去极化，包括新颖的多光谱光学和光声组织分析

• 批准号: 462569370
• 负责人: Professorin Dr.-Ing. Lena Maier-Hein, Ph.D.
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/462569370?language=en
• 关键词: Blocking; modulation; Spreading; Depolarisations; gyrencephalic

Spreading depolarisation (SD) is a novel identified mechanism that produces secondary damage and neuronal death in critically ill neurological patients, including subarachnoid haemorrhage, ischaemic stroke and head trauma. Preliminary clinical and experimental data indicates that SD can be inhibited in both lissencephalic and gyrencephalic brains and that the damage can be reduced by 50%, but under certain conditions the therapy could become ineffective. Unfortunately, the lack of adequate imaging methods hampers neuroprotective research to date. There is still a missing link between successful neuroprotective therapies in small animal models and effective therapies in humans. Using our well-established gyrencephalic animal translational models developed by our research group, and in a new proposed model that permits a fine clinical evaluation at 3 weeks, we can study and characterise the efficacy of various neuroprotective medications currently used in humans for other purposes.The goals of this project are (1) the establishment of a new multimodal imaging concept to characterise SDs and (2) the comparative evaluation of therapies for SD inhibition and attenuation and their efficacy as neuroprotective therapies in translational animal models.Our research methods are based on multiparametric monitoring using electrocorticography (ECoG) and wireless ECoG combined with multispectral optical imaging and photoacoustic imaging. Characterisation of the haemodynamic responses and their consequences will be achieved by determining oxygenation, blood volume, blood flow and velocities, vascular reactivity, brain/infarct size and brain connectivity via multimodal image analysis. For the first time, these parameters can be determined deep inside the tissue, thus enabling the three dimensional characterisation of brain infarction and SDs. Based on the novel imaging concept, a gyrencephalic animal model will be used to study various therapeutic regimens. An important goal is to find the best combination of therapies that either block SDs or attenuate their worst haemodynamic phases and to quantify the infarct size reduction resulting from the best combined treatment in a stroke model. The knowledge generated by this project will tackle the missing neuroprotective translation from animal models into patients, and the use of approved medications will enable an immediate, better planning and execution of a successful future clinical trial in humans.

扩散去极化（SD）是一种新发现的机制，可在危重神经系统患者中产生继发性损伤和神经元死亡，包括蛛网膜下腔出血、缺血性中风和头部外伤。初步临床和实验数据表明，SD在无脑和环脑中均可被抑制，损伤可减少50%，但在某些条件下治疗可能会变得无效。不幸的是，迄今为止，缺乏足够的成像方法阻碍了神经保护研究。小动物模型中成功的神经保护疗法与人类的有效疗法之间仍然存在缺失的联系。利用我们研究小组开发的完善的环脑动物转化模型，以及在允许 3 周内进行精细临床评估的新提出的模型中，我们可以研究和表征目前用于人类的各种神经保护药物用于其他目的的功效。该项目的目标是 (1) 建立新的多模态成像概念来表征 SD，以及 (2) 对 SD 抑制和治疗的比较评估 衰减及其在转化动物模型中作为神经保护疗法的功效。我们的研究方法基于使用皮质电图（ECoG）和无线ECoG结合多光谱光学成像和光声成像的多参数监测。 通过多模态图像分析确定氧合、血容量、血流量和速度、血管反应性、脑/梗死面积和脑连接性，可以实现血流动力学反应及其后果的表征。首次可以在组织深处确定这些参数，从而实现脑梗塞和 SD 的三维表征。基于新颖的成像概念，环脑动物模型将用于研究各种治疗方案。一个重要的目标是找到阻止 SD 或减弱其最差血流动力学阶段的最佳治疗组合，并量化中风模型中最佳组合治疗所导致的梗塞面积减少。该项目产生的知识将解决从动物模型到患者的缺失神经保护翻译，并且使用批准的药物将能够立即、更好地规划和执行未来成功的人类临床试验。