Department of Electrical and Computer Engineering, Rice University, Houston, USA; Rice Neuroengineering Initiative, Rice University, Houston, USA.
Rice Neuroengineering Initiative, Rice University, Houston, USA; Applied Physics Graduate Program, Rice University, Houston, USA.
Biomaterials. 2022 Dec;291:121905. doi: 10.1016/j.biomaterials.2022.121905. Epub 2022 Nov 14.
Flexible neural electrodes improve the recording longevity and quality of individual neurons by promoting tissue-electrode integration. However, the intracortical implantation of flexible electrodes inevitably induces tissue damage. Understanding the longitudinal neural and vascular recovery following the intracortical implantation is critical for the ever-growing applications of flexible electrodes in both healthy and disordered brains. Aged animals are of particular interest because they play a key role in modeling neurological disorders, but their tissue-electrode interface remains mostly unstudied. Here we integrate in-vivo two-photon imaging and electrophysiological recording to determine the time-dependent neural and vascular dynamics after the implantation of ultraflexible neural electrodes in aged mice. We find heightened angiogenesis and vascular remodeling in the first two weeks after implantation, which coincides with the rapid increase in local field potentials and unit activities detected by electrophysiological recordings. Vascular remodeling in shallow cortical layers preceded that in deeper layers, which often lasted longer than the recovery of neural signals. By six weeks post-implantation vascular abnormalities had subsided, resulting in normal vasculature and microcirculation. Putative cell classification based on firing pattern and waveform shows similar recovery time courses in fast-spiking interneurons and pyramidal neurons. These results elucidate how structural damages and remodeling near implants affecting recording efficacy, and support the application of ultraflexible electrodes in aged animals at minimal perturbations to endogenous neurophysiology.
柔性神经电极通过促进组织-电极整合，提高了单个神经元的记录寿命和质量。然而，柔性电极的脑内植入不可避免地会引起组织损伤。了解脑内植入后神经和血管的纵向恢复情况，对于柔性电极在健康和病变大脑中的应用至关重要。老年动物尤其有趣，因为它们在模拟神经疾病方面发挥着关键作用，但它们的组织-电极界面在很大程度上仍未得到研究。在这里，我们整合了体内双光子成像和电生理记录，以确定超柔性神经电极植入老年小鼠后脑内的时间依赖性神经和血管动力学。我们发现，在植入后的前两周内，血管生成和血管重塑加剧，这与通过电生理记录检测到的局部场电位和单位活动的快速增加相一致。浅层皮层中的血管重塑先于深层皮层中的血管重塑，且这种重塑持续时间往往长于神经信号的恢复。到植入后 6 周，血管异常已经消退，导致血管正常化和微循环正常化。基于放电模式和波形的假定细胞分类表明，快速放电中间神经元和锥体细胞的恢复时间过程相似。这些结果阐明了植入物附近的结构损伤和重塑如何影响记录效果，并支持在最小干扰内源性神经生理学的情况下，将超柔性电极应用于老年动物。
