Department of Neuroscience, University of Florida, Gainesville, FL, United States of America.
J Neural Eng. 2018 Dec;15(6):066027. doi: 10.1088/1741-2552/aae4b6. Epub 2018 Sep 27.
Neuroinflammation has long been associated with the performance decline of intracortical microelectrodes (IMEs). Consequently, several strategies, including the use of anti-inflammatories, have been employed to mitigate the inflammation surrounding IMEs. However, these strategies have had limited success towards achieving a chronically viable cortical neural interface, questioning the efficacy of anti-inflammatory approach.
Herein, we conducted a systematic study in rats implanted with functional devices by modulating inflammation via systemic injection of lipopolysaccharide (LPS), dexamethasone (DEX), a combination of both, or none to assess the degree of inflammation on device functionality. We hypothesized that implanted rats treated with LPS will have a negative impact, and rats treated with DEX will have a positive impact on functionality IMEs and histological outcome.
Contrary to our hypothesis, we did not observe adverse effects in recording metrics among different groups with LPS and/or DEX treatment despite alterations in initial pro-inflammatory markers. We also did not observe any functional benefit of anti-inflammatory treatment. Regardless of the treatment conditions, the recording quality degraded at chronic time points. In end-point histology, implanted rats that received LPS had significantly lower NeuN density and higher levels of CD68 surrounding the implant site, indicative of the pro-inflammatory effect of LPS, which, however, contradicted with the recorded results.
Collectively, our results suggest that acute inflammatory events may not be the key driver for functional degradation of IMEs. Future intervention strategies geared towards improving the functional longevity of intracortical devices may benefit using multi-modal approaches rather than a single approach, such as controlling the initial inflammatory response.
神经炎症与皮层内微电极（IMEs）性能下降长期相关。因此，人们采用了几种策略，包括使用抗炎药，以减轻围绕 IMEs 的炎症。然而，这些策略在实现长期可行的皮层神经接口方面收效甚微，这对抗炎方法的疗效提出了质疑。
在这里，我们通过对植入功能性设备的大鼠进行系统研究，通过全身注射脂多糖（LPS）、地塞米松（DEX）、两者的组合或不注射来调节炎症，以评估炎症对设备功能的影响程度。我们假设，用 LPS 处理的植入大鼠将产生负面影响，而用 DEX 处理的大鼠将对 IMEs 的功能和组织学结果产生积极影响。
与我们的假设相反，尽管初始促炎标志物发生了变化，但我们在 LPS 和/或 DEX 处理的不同组中没有观察到记录指标的不良影响。我们也没有观察到抗炎治疗的任何功能益处。无论治疗条件如何，在慢性时间点，记录质量都会下降。在终点组织学上，接受 LPS 治疗的植入大鼠在植入部位周围的 NeuN 密度明显较低，CD68 水平较高，表明 LPS 的促炎作用，但这与记录结果相矛盾。
总的来说，我们的结果表明，急性炎症事件可能不是 IMEs 功能退化的关键驱动因素。未来旨在提高皮层内设备功能耐久性的干预策略可能受益于采用多模态方法，而不是单一方法，例如控制初始炎症反应。
