OBJECTIVE Neuroprosthetics hold tremendous promise to restore function through brain-computer interfaced devices. However, clinical applications of implantable microelectrodes remain limited given the challenges of maintaining neuronal signals for extended periods of time and with multiple biological mechanisms negatively affecting electrode performance. Acute and chronic inflammation, oxidative stress, and blood brain barrier disruption contribute to inconsistent electrode performance. We hypothesized that therapeutic hypothermia (TH) applied at the microelectrode insertion site will positively modulate both inflammatory and apoptotic pathways, promoting neuroprotection and improved performance in the long-term. APPROACH A custom device and thermoelectric system were designed to deliver controlled TH locally to the cortical implant site at the time of microelectrode array insertion and immediately following surgery. The TH paradigm was derived from in vivo cortical temperature measurements and finite element modeling of temperature distribution profiles in the cortex. Male Sprague-Dawley rats were implanted with non-functional Utah microelectrodes arrays (UMEA) consisting of 4 × 4 grid of 1.5 mm long parylene-coated silicon shanks. In one group, TH was applied to the implant site for two hours following the UMEA implantation, while the other group was implanted under normothermic conditions without treatment. At 48 h, 72 h, 7 d and 14 d post-implantation, mRNA expression levels for genes associated with inflammation and apoptosis were compared between normothermic and hypothermia-treated groups. MAIN RESULTS The custom system delivered controlled TH to the cortical implant site and the numerical models confirmed that the temperature decrease was confined locally. Furthermore, a one-time application of TH post UMEA insertion significantly reduced the acute inflammatory response with a reduction in the expression of inflammatory regulating cytokines and chemokines. SIGNIFICANCE This work provides evidence that acutely applied hypothermia is effective in significantly reducing acute inflammation post intracortical electrode implantation.

中文翻译：

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低温治疗可以减少与犹他州阵列植入物相关的皮质炎症。

目的神经假体具有通过脑机接口设备恢复功能的巨大前景。然而，鉴于维持神经元信号延长时间以及具有多种负面影响电极性能的生物学机制的挑战，植入式微电极的临床应用仍然受到限制。急性和慢性炎症，氧化应激和血脑屏障破坏导致电极性能不一致。我们假设在微电极插入部位应用治疗性低温（TH）将积极调节炎症和凋亡途径，长期促进神经保护并改善性能。方法定制设备和热电系统旨在在微电极阵列插入时以及手术后立即将受控的TH局部输送到皮质植入物位置。TH范式源自体内皮质温度测量和皮质温度分布曲线的有限元建模。将雄性Sprague-Dawley大鼠植入无功能的犹他州微电极阵列（UMEA），该阵列由4×4网格的1.5毫米长聚对二甲苯涂覆的硅杆组成。一组在UMEA植入后将TH应用于植入部位两个小时，而另一组则在正常温度下未经治疗植入。植入后48小时，72小时，7 d和14 d，比较了常温和低温治疗组与炎症和凋亡相关基因的mRNA表达水平。主要结果定制系统将可控制的TH传递至皮质植入物部位，数值模型证实温度下降仅限于局部。此外，在UMEA插入后一次性应用TH可显着减少急性炎症反应，并减少炎症调节细胞因子和趋化因子的表达。意义这项工作提供了证据，表明急性应用低温可以有效地减少皮层内电极植入术后的急性炎症。主要结果定制系统将可控制的TH传递至皮质植入物部位，数值模型证实温度下降仅限于局部。此外，在UMEA插入后一次性应用TH可显着减少急性炎症反应，并减少炎症调节细胞因子和趋化因子的表达。意义这项工作提供了证据，表明急性应用低温可以有效地减少皮层内电极植入术后的急性炎症。主要结果定制系统将可控制的TH输送至皮质植入物部位，数值模型证实温度下降仅限于局部。此外，在UMEA插入后一次性应用TH可显着减少急性炎症反应，并减少炎症调节细胞因子和趋化因子的表达。意义这项工作提供了证据，表明急性应用低温可以有效地减少皮层内电极植入术后的急性炎症。