Wellman Steven M, Guzman Kelly, Stieger Kevin C, Brink Lauren E, Sridhar Sadhana, Dubaniewicz Mitchell T, Li Lehong, Cambi Franca, Kozai Takashi D Y
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neural Basis of Cognition, Pittsburgh, PA, USA.
Veterans Administration Pittsburgh, Pittsburgh, PA, USA.
Biomaterials. 2020 May;239:119842. doi: 10.1016/j.biomaterials.2020.119842. Epub 2020 Feb 6.
Biological inflammation induced during penetrating cortical injury can disrupt functional neuronal and glial activity within the cortex, resulting in potential recording failure of chronically implanted neural interfaces. Oligodendrocytes provide critical support for neuronal health and function through direct contact with neuronal soma and axons within the cortex. Given their fundamental role to regulate neuronal activity via myelin, coupled with their heightened vulnerability to metabolic brain injury due to high energetic demands, oligodendrocytes are hypothesized as a possible source of biological failure in declining recording performances of intracortical microelectrode devices. To determine the extent of their contribution to neuronal activity and function, a cuprizone-inducible model of oligodendrocyte depletion and demyelination in mice was performed prior to microelectrode implantation. At 5 weeks of cuprizone exposure, mice demonstrated significantly reduced cortical oligodendrocyte density and myelin expression. Mice were then implanted with functional recording microelectrodes in the visual cortex and neuronal activity was evaluated up to 7 weeks alongside continued cuprizone administration. Cuprizone-induced oligodendrocyte loss and demyelination was associated with significantly reduced recording performances at the onset of implantation, which remained relatively stable over time. In contast, recording performances for mice on a normal diet were intially elevated before decreasing over time to the recording level of tcuprizone-treated mice. Further electrophysiological analysis revealed deficits in multi-unit firing rates, frequency-dependent disruptions in neuronal oscillations, and altered laminar communication within the cortex of cuprizone-treated mice. Post-mortem immunohistochemistry revealed robust depletion of oligodendrocytes around implanted microelectrode arrays alongside comparable neuronal densities to control mice, suggesting that oligodendrocyte loss was a possible contributor to chronically impaired device performances. This study highlights potentially significant contributions from the oligodendrocyte lineage population concerning the biological integration and long-term functional performance of neural interfacing technology.
穿透性皮质损伤期间诱发的生物炎症会破坏皮质内功能性神经元和神经胶质细胞的活动，导致长期植入的神经接口出现潜在的记录失败。少突胶质细胞通过与皮质内的神经元胞体和轴突直接接触，为神经元的健康和功能提供关键支持。鉴于它们通过髓鞘调节神经元活动的基本作用，以及由于高能量需求而对代谢性脑损伤的高度易感性，少突胶质细胞被认为是导致皮质内微电极装置记录性能下降的生物故障的可能来源。为了确定它们对神经元活动和功能的贡献程度，在微电极植入前，对小鼠进行了一种用铜螯合剂诱导的少突胶质细胞耗竭和脱髓鞘模型实验。在接触铜螯合剂5周时，小鼠的皮质少突胶质细胞密度和髓鞘表达显著降低。然后将功能性记录微电极植入小鼠视觉皮质，并在持续给予铜螯合剂的情况下，对神经元活动进行长达7周的评估。铜螯合剂诱导的少突胶质细胞丢失和脱髓鞘与植入开始时记录性能的显著降低有关，且随着时间推移相对保持稳定。相比之下，正常饮食小鼠的记录性能最初有所提高，之后随时间下降至铜螯合剂处理小鼠的记录水平。进一步的电生理分析显示，铜螯合剂处理小鼠的多单位放电率存在缺陷、神经元振荡出现频率依赖性破坏以及皮质内的层间通讯改变。死后免疫组织化学显示，植入的微电极阵列周围少突胶质细胞大量耗竭，而神经元密度与对照小鼠相当，这表明少突胶质细胞丢失可能是导致设备性能长期受损的原因。这项研究突出了少突胶质细胞谱系群体对神经接口技术的生物整合和长期功能性能的潜在重大贡献。
