Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen and University Clinic, Tübingen, Germany.
Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University Tübingen and University Clinic, Tübingen, Germany.
Mol Imaging Biol. 2023 Apr;25(2):363-374. doi: 10.1007/s11307-022-01764-8. Epub 2022 Sep 8.
Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for ischemic stroke such as hypertension, dyslipidemia, diabetes, and smoking. The role of inhibitory G protein-dependent receptor (GPCR) signaling in regulating cerebrovascular functions remains largely elusive. We examined the importance of GPCR signaling in cerebral blood flow (CBF) and its stability after sudden interruption using various in vivo high-resolution magnetic resonance imaging techniques. To this end, we induced a functional knockout of GPCR signaling in the brain vasculature by injection of pertussis toxin (PTX). Our results show that PTX induced global brain hypoperfusion and microvascular collapse. When PTX-pretreated animals underwent transient unilateral occlusion of one common carotid artery, CBF was disrupted in the ipsilateral hemisphere resulting in the collapse of the cortically penetrating microvessels. In addition, pronounced stroke features in the affected brain regions appeared in both MRI and histological examination. Our findings suggest an impact of cerebrovascular GPCR signaling in the maintenance of CBF, which may be useful for novel pharmacotherapeutic approaches to prevent and treat cerebrovascular dysfunction and stroke.
脑灌注不足和血管功能障碍与缺血性中风的常见危险因素密切相关，如高血压、血脂异常、糖尿病和吸烟。抑制性 G 蛋白依赖性受体 (GPCR) 信号在调节脑血管功能中的作用在很大程度上仍不清楚。我们使用各种体内高分辨率磁共振成像技术研究了 GPCR 信号在脑血流 (CBF) 及其在突然中断后的稳定性中的重要性。为此，我们通过注射百日咳毒素 (PTX) 诱导脑血管中 GPCR 信号的功能性敲除。我们的结果表明，PTX 诱导全脑灌注不足和微血管塌陷。当接受 PTX 预处理的动物经历单侧颈总动脉短暂阻塞时，CBF 在同侧半球中断，导致皮质穿透微血管塌陷。此外，在 MRI 和组织学检查中，受影响的大脑区域都出现了明显的中风特征。我们的研究结果表明，脑血管 GPCR 信号在维持 CBF 方面具有重要作用，这可能有助于开发新的药物治疗方法，以预防和治疗脑血管功能障碍和中风。
