Gauberti Maxime, Montagne Axel, Quenault Aurélien, Vivien Denis
Inserm, Inserm UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Université de Caen Basse-Normandie - GIP Cyceron Caen, France.
Front Cell Neurosci. 2014 Nov 27;8:389. doi: 10.3389/fncel.2014.00389. eCollection 2014.
Although the blood-brain barrier (BBB) was thought to protect the brain from the effects of the immune system, immune cells can nevertheless migrate from the blood to the brain, either as a cause or as a consequence of central nervous system (CNS) diseases, thus contributing to their evolution and outcome. Accordingly, as the interface between the CNS and the peripheral immune system, the BBB is critical during neuroinflammatory processes. In particular, endothelial cells are involved in the brain response to systemic or local inflammatory stimuli by regulating the cellular movement between the circulation and the brain parenchyma. While neuropathological conditions differ in etiology and in the way in which the inflammatory response is mounted and resolved, cellular mechanisms of neuroinflammation are probably similar. Accordingly, neuroinflammation is a hallmark and a decisive player of many CNS diseases. Thus, molecular magnetic resonance imaging (MRI) of inflammatory processes is a central theme of research in several neurological disorders focusing on a set of molecules expressed by endothelial cells, such as adhesion molecules (VCAM-1, ICAM-1, P-selectin, E-selectin, …), which emerge as therapeutic targets and biomarkers for neurological diseases. In this review, we will present the most recent advances in the field of preclinical molecular MRI. Moreover, we will discuss the possible translation of molecular MRI to the clinical setting with a particular emphasis on myeloperoxidase imaging, autologous cell tracking, and targeted iron oxide particles (USPIO, MPIO).
尽管血脑屏障(BBB)被认为可保护大脑免受免疫系统的影响,但免疫细胞仍可从血液迁移至大脑,这既可能是中枢神经系统(CNS)疾病的病因,也可能是其结果,从而影响疾病的发展和转归。因此,作为中枢神经系统与外周免疫系统之间的界面,血脑屏障在神经炎症过程中至关重要。特别是,内皮细胞通过调节循环与脑实质之间的细胞移动,参与大脑对全身或局部炎症刺激的反应。虽然神经病理状况在病因以及炎症反应的发生和消退方式上有所不同,但神经炎症的细胞机制可能相似。因此,神经炎症是许多中枢神经系统疾病的一个标志和决定性因素。因此,炎症过程的分子磁共振成像(MRI)是几种神经系统疾病研究的核心主题,其聚焦于内皮细胞表达的一组分子,如黏附分子(血管细胞黏附分子-1、细胞间黏附分子-1、P-选择素、E-选择素等),这些分子已成为神经疾病的治疗靶点和生物标志物。在本综述中,我们将介绍临床前分子MRI领域的最新进展。此外,我们将讨论分子MRI向临床应用转化的可能性,特别强调髓过氧化物酶成像、自体细胞追踪和靶向氧化铁颗粒(超顺磁性氧化铁、多聚体氧化铁)。