Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Gladstone Institutes, San Francisco, CA, USA.
Exp Neurol. 2019 Dec;322:113046. doi: 10.1016/j.expneurol.2019.113046. Epub 2019 Aug 28.
Imaging the dynamic interactions between immune cells, glia, neurons and the vasculature in living rodents has revolutionized our understanding of physiological and pathological mechanisms of the CNS. Emerging microscopy and imaging technologies have enabled longitudinal tracking of structural and functional changes in a plethora of different cell types in the brain. The development of novel methods also allowed stable and longitudinal optical access to the spinal cord with minimum tissue perturbation. These important advances facilitated the application of in vivo imaging using two-photon microscopy for studies of the healthy, diseased, or injured spinal cord. Indeed, decoding the interactions between peripheral and resident cells with the spinal cord vasculature has shed new light on neuroimmune and vascular mechanisms regulating the onset and progression of neurological diseases. This review focuses on imaging studies of the interactions between the vasculature and peripheral immune cells or microglia, with emphasis on their contribution to neuroinflammation. We also discuss in vivo imaging studies highlighting the importance of neurovascular changes following spinal cord injury. Real-time imaging of blood-brain barrier (BBB) permeability and other vascular changes, perivascular glial responses, and immune cell entry has revealed unanticipated cellular mechanisms and novel molecular pathways that can be targeted to protect the injured or diseased CNS. Imaging the cell-cell interactions between the vasculature, immune cells, and neurons as they occur in real time, is a powerful tool both for testing the efficacy of existing therapeutic approaches, and for identifying new targets for limiting damage or enhancing the potential for repair of the affected spinal cord tissue.
在活体啮齿动物中成像免疫细胞、神经胶质细胞、神经元和脉管系统之间的动态相互作用，彻底改变了我们对中枢神经系统生理和病理机制的理解。新兴的显微镜和成像技术使我们能够对大脑中大量不同类型的细胞的结构和功能变化进行长期跟踪。新方法的发展还允许对脊髓进行稳定和长期的光学访问，而对组织的干扰最小。这些重要的进展促进了使用双光子显微镜对健康、患病或受伤的脊髓进行体内成像的应用。事实上，解码外周细胞和驻留细胞与脊髓脉管系统之间的相互作用，为调节神经免疫和血管机制的神经疾病的发生和进展提供了新的认识。本综述重点介绍了血管系统与外周免疫细胞或小胶质细胞相互作用的成像研究，强调了它们对神经炎症的贡献。我们还讨论了强调脊髓损伤后神经血管变化重要性的体内成像研究。实时成像血脑屏障 (BBB) 通透性和其他血管变化、血管周围神经胶质反应以及免疫细胞进入，揭示了意想不到的细胞机制和新的分子途径，这些途径可以作为保护受损或患病中枢神经系统的靶点。实时成像血管系统、免疫细胞和神经元之间的细胞-细胞相互作用是一种强大的工具，既可以测试现有治疗方法的疗效，也可以确定限制损伤或增强受影响脊髓组织修复潜力的新靶点。
