ARC Centre of Excellence in Nanoscale Biophotonics (CNBP), Macquarie University, Sydney, Australia.
Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Brain Behav Immun. 2018 Jul;71:18-22. doi: 10.1016/j.bbi.2018.04.011. Epub 2018 Apr 17.
Mounting evidence indicates that cytokines secreted by innate immune cells in the brain play a central role in regulating neural circuits that subserve mood, cognition, and sickness responses. A major impediment to the study of neuroimmune signaling in healthy and disease states is the absence of tools for in vivo detection of cytokine release in the brain. Here we describe the design and application of a cytokine detection device capable of serial monitoring of local cytokine release in discrete brain regions. The immunocapture device consisted of a modified optical fiber labeled with a capture antibody specific for the pro-inflammatory cytokine interleukin-1 beta (IL-1β). Using a sandwich immunoassay method, in vitro data demonstrate that the sensing interface of the modified optical fiber has a linear detection range of 3.9 pg mL-500 pg mL and spatial resolution on the order of 200-450 μm. Finally, we show that the immunocapture device can be introduced into a perforated guide cannula for repeated analyte measurements in vivo. An increase in fluorescence detection of spatially localized intrahippocampal IL-1β release was observed following a peripheral lipopolysaccharide challenge in Sprague-Dawley rats. This novel immunosensing technology represents an opportunity for unlocking the function of neuroimmune signaling.
越来越多的证据表明,大脑中固有免疫细胞分泌的细胞因子在调节情绪、认知和疾病反应的神经回路中发挥着核心作用。在健康和疾病状态下研究神经免疫信号的一个主要障碍是缺乏用于体内检测大脑中细胞因子释放的工具。在这里,我们描述了一种细胞因子检测装置的设计和应用,该装置能够连续监测离散脑区的局部细胞因子释放。免疫捕获装置由一根经过修饰的光纤组成,光纤上标记有针对促炎细胞因子白细胞介素-1β(IL-1β)的捕获抗体。通过夹心免疫测定法,体外数据表明,修饰光纤的传感界面具有 3.9pg/mL-500pg/mL 的线性检测范围和 200-450μm 左右的空间分辨率。最后,我们表明,免疫捕获装置可以被引入穿孔引导套管中,以便在体内进行重复分析物测量。在 Sprague-Dawley 大鼠中,外周脂多糖刺激后,观察到空间定位的海马内白细胞介素-1β释放的荧光检测增加。这种新型免疫传感技术为揭示神经免疫信号的功能提供了机会。