Ikeda Hiroyuki, Ishii Akira, Sano Kohei, Chihara Hideo, Arai Daisuke, Abekura Yu, Nishi Hidehisa, Ono Masahiro, Saji Hideo, Miyamoto Susumu
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Front Neurosci. 2020 Apr 22;14:370. doi: 10.3389/fnins.2020.00370. eCollection 2020.
Chronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), with macrophages playing a key role in the process. The present study evaluated visualization of macrophages present in CAs using an activatable fluorescent probe (IONP-ICG) comprising an iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG).
IONP-ICG was intravenously administered to 15-week-old CA model rats ( = 8), and near-infrared fluorescence (NIRF) imaging and histological assessment of exposed CAs and cerebral arteries were performed 48 h later. Similar evaluations were performed in the control group, which included CA model rats given IONPs or ICG ( = 8 each).
ICG-derived NIRF signals were detected in three IONP-ICG group rats but not in IONP or ICG control groups. Among the three rats that exhibited signals, NIRF signal accumulation was observed in the CA of two rats and at the site of hemodynamic stress in the left posterior cerebral artery in one rat. Histologically, NIRF signals correlated strongly with macrophage localization. A total of 13 CAs formed in the IONP-ICG group. The number of macrophages in the CA wall was significantly greater in the two CAs that exhibited NIRF signals compared to the remaining 11 CAs that did not ( = 0.037). Moreover, all 11 CAs that did not exhibit NIRF signals were iron-negative, while the two CAs that exhibited NIRF signals were both iron-positive ( = 0.013).
NIRF imaging using an activatable IONP-ICG probe is feasible for detecting the macrophage-rich regions in CAs and the cerebral artery wall, which is considered an early lesion in the process of CA formation.
慢性炎症参与脑动脉瘤（CA）的形成和扩大，巨噬细胞在此过程中起关键作用。本研究使用一种可激活的荧光探针（IONP-ICG）评估CA中存在的巨噬细胞的可视化情况，该探针由与吲哚菁绿（ICG）偶联的氧化铁纳米颗粒（IONP）组成。
将IONP-ICG静脉注射到15周龄的CA模型大鼠（n = 8）中，48小时后对暴露的CA和脑动脉进行近红外荧光（NIRF）成像和组织学评估。在对照组中进行了类似的评估，对照组包括给予IONP或ICG的CA模型大鼠（每组n = 8）。
在三只IONP-ICG组大鼠中检测到ICG衍生的NIRF信号，而在IONP或ICG对照组中未检测到。在显示信号的三只大鼠中，在两只大鼠的CA中观察到NIRF信号积累，在一只大鼠的左大脑后动脉血流动力学应激部位观察到NIRF信号积累。组织学上，NIRF信号与巨噬细胞定位密切相关。IONP-ICG组共形成13个CA。与其余11个未显示NIRF信号的CA相比，在显示NIRF信号的两个CA中，CA壁中的巨噬细胞数量明显更多（P = 0.037）。此外，所有11个未显示NIRF信号的CA均为铁阴性，而两个显示NIRF信号的CA均为铁阳性（P = 0.013）。
使用可激活的IONP-ICG探针进行NIRF成像可用于检测CA和脑动脉壁中富含巨噬细胞的区域，这被认为是CA形成过程中的早期病变。
