Neurovascular Research Unit, Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid and Instituto de Investigación Hospital 12 de Octubre i+12, Madrid, Spain.
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
J Cereb Blood Flow Metab. 2021 Jul;41(7):1692-1706. doi: 10.1177/0271678X20976412. Epub 2020 Dec 1.
Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes.
中风主要影响老年人和合并症患者,但这些方面尚未得到充分考虑。由于血管生成/血管发生是中风恢复的关键过程,我们旨在使用代谢综合征啮齿动物模型,通过动态对比增强磁共振成像(DCE-MRI)来评估其非侵入性潜力,以确定不同合并症如何影响结果和血管生成/血管发生。我们使用了肥胖(JCR:LA-Cp/Cp)和瘦鼠,20/22 月龄的肥胖(JCR:LA-Cp/Cp)是代谢综合征的模型。在通过短暂性 MCAO 诱导实验性缺血后,通过组织学分析血管生成,通过流式细胞术测定外周血中的内皮祖细胞来确定血管发生,并在 tMCAO 后 3、7 和 28 天评估它们在培养中的促血管生成特性和血管功能通过 DCE-MRI。我们的结果显示,与瘦鼠相比,肥胖鼠的梗死体积增加、BBB 损伤和预后不良。肥胖鼠的中风后血管生成/血管发生也较差,这一结果转化为 DCE-MRI 确定的血管功能受损。这些数据证实,老年大鼠中风引起的结果和血管生成/血管发生受到肥胖基因型中存在的合并症的负面影响,并且 DCE-MRI 可能是评估血管功能和血管生成过程的非侵入性技术。