Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):5894-5899. doi: 10.1073/pnas.1705509114. Epub 2017 May 22.
Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2-12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.
将电探针植入大脑一直是神经科学研究和生物医学应用的核心,尽管传统探针会在周围组织中引起神经胶质增生。我们最近报道了通过注射器注射将超柔韧的开放式网格电子产品植入啮齿动物大脑的方法,这种方法表现出了有前景的慢性组织反应和记录稳定性。在这里,我们报告了网格电子产品/脑组织界面的随时间变化的组织学研究结果,这些研究结果来自与探针长轴垂直和平行的切片,同时还报告了传统的柔性薄膜探针的研究结果。包含网格电子产品的垂直和平行脑切片的共聚焦荧光显微镜图像显示,星形胶质细胞、小胶质细胞和神经元的分布在 2-12 周内变得均匀,而柔性薄膜探针在同一时期会导致星形胶质细胞和小胶质细胞的明显积累和神经元的减少。4 周和 12 周数据的定量分析表明,从网格电子产品表面到远离探针的基线,神经元、轴突、星形胶质细胞和小胶质细胞的信号几乎相同,而与柔性聚合物探针相反,后者显示神经元信号减少,星形胶质细胞和小胶质细胞信号增加。值得注意的是,包含几乎整个网格电子产品探针的矢状脑切片的图像显示,组织界面是均匀的,神经元和神经丝在植入后 3 个月穿过网格。超柔韧开放式网格电子产品探针植入后实现的最小免疫反应和与脑组织的无缝界面为体内慢性记录和大脑活动的调制提供了巨大的优势,并可能在未来带来广泛的机会。