PDF(Pubmed)
Abstract：
Reperfusion therapies in acute ischemic stroke have demonstrated their efficacy in promoting clinical recovery. However, ischemia/reperfusion injury and related inflammation remain a major challenge in patient clinical management. We evaluated the spatio-temporal evolution of inflammation using sequential clinical [11C]PK11195 PET-MRI in a non-human primate (NHP) stroke model mimicking endovascular thrombectomy (EVT) with a neuroprotective cyclosporine A (CsA) treatment. The NHP underwent a 110-min transient endovascular middle cerebral artery occlusion. We acquired [11C]PK11195 dynamic PET-MR imaging at baseline, 7 and 30 days after intervention. Individual voxel-wise analysis was performed thanks to a baseline scan database. We quantified [11C]PK11195 in anatomical regions and in lesioned areas defined on per-occlusion MR diffusion-weighted imaging and perfusion [15O2]H2OPET imaging. [11C]PK11195 parametric maps showed a clear uptake overlapping the lesion core at D7, which further increased at D30. Voxel-wise analysis identified individuals with significant inflammation at D30, with voxels located within the most severe diffusion reduction area during occlusion, mainly in the putamen. The quantitative analysis revealed that thalamic inflammation lasted until D30 and was significantly reduced in the CsA-treated group compared to the placebo. In conclusion, we showed that chronic inflammation matched ADC decrease at occlusion time, a region exposed to an initial burst of damage-associated molecular patterns, in an NHP stroke model mimicking EVT. We described secondary thalamic inflammation and the protective effect of CsA in this region. We propose that major ADC drop in the putamen during occlusion may identify individuals who could benefit from early personalized treatment targeting inflammation.
摘要：
急性缺血性卒中的再灌注治疗已证明其在促进临床恢复方面的功效。然而,缺血/再灌注损伤和相关炎症仍然是患者临床治疗的主要挑战.我们使用序贯临床[11C]PK11195PET-MRI在非人灵长类动物（NHP）中风模型中评估了炎症的时空演变，该模型模拟了血管内血栓切除术（EVT）和神经保护性环孢素A（CsA）治疗。NHP经历了110分钟的短暂性血管内大脑中动脉闭塞。我们在基线时获得了[11C]PK11195动态PET-MR成像，干涉后7和30天。由于基线扫描数据库,进行个体体素分析。我们在每次闭塞MR扩散加权成像和灌注[15O2]H2OPET成像上定义的解剖区域和病变区域中定量了[11C]PK11195。[11C]PK11195参数图显示在D7处与病变核心重叠的清晰摄取，在D30处进一步增加。按体素分析确定在D30时具有显著炎症的个体,在闭塞期间体素位于最严重的扩散减少区域内,主要在壳核中。定量分析显示丘脑炎症持续到D30,并且与安慰剂相比,CsA治疗组显著降低。总之,我们显示，慢性炎症匹配ADC在闭塞时间降低，暴露于与损伤相关的分子模式的初始爆发的区域，在模拟EVT的NHP中风模型中。我们描述了继发性丘脑炎症和CsA在该区域的保护作用。我们建议在闭塞过程中壳核的主要ADC下降可能会识别出可以从早期针对炎症的个性化治疗中受益的个体。
