Noel Rebecca L, Kline-Schoder Alina R, Batts Alec J, Kwon Nancy, Tsitsos Fotios, Konofagou Elisa E
Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Department of Radiology, Columbia University, New York, NY, USA.
iScience. 2025 Jul 22;28(8):113173. doi: 10.1016/j.isci.2025.113173. eCollection 2025 Aug 15.
Focused ultrasound-induced blood-brain barrier opening (FUS-BBBO) is a well-established neuroimmune modulation and drug delivery enhancement tool capable of effecting cellular, cognitive, and pathological benefits in the brain. However, the cellular mechanisms underlying these bioeffects remain incompletely characterized, motivating the present study investigating the role of a critical glial cell type: astrocytes. Here, we use single-cell RNA sequencing and flow cytometry to characterize the phenotypic response of hippocampal astrocytes 2, 4, and 7 days after FUS-BBBO exposure in aged WT and Alzheimer's disease mice. The data presented herein indicate that FUS-BBBO increases gene expression related to synapse modification, neurogenesis, ion transport, and neuronal development. Taken together, these data elucidate a glioprotective role for hippocampal astrocytes following FUS-BBBO, offering mechanistic context and support for previously observed benefits of FUS-BBBO. This evidence critically deepens our understanding of the cellular effects of FUS-BBBO as clinical adoption becomes more widespread.
聚焦超声诱导的血脑屏障开放（FUS-BBBO）是一种成熟的神经免疫调节和药物递送增强工具，能够在大脑中产生细胞、认知和病理方面的益处。然而，这些生物效应背后的细胞机制仍未完全明确，这促使本研究探究一种关键神经胶质细胞类型——星形胶质细胞的作用。在此，我们使用单细胞RNA测序和流式细胞术来表征老年野生型和阿尔茨海默病小鼠在接受FUS-BBBO照射后2天、4天和7天海马星形胶质细胞的表型反应。本文提供的数据表明，FUS-BBBO可增加与突触修饰、神经发生、离子转运和神经元发育相关的基因表达。综上所述，这些数据阐明了FUS-BBBO后海马星形胶质细胞的神经胶质保护作用，为先前观察到的FUS-BBBO的益处提供了机制背景和支持。随着FUS-BBBO在临床上的应用越来越广泛，这一证据极大地加深了我们对其细胞效应的理解。
