Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. Department of Medicine, Platform of Translational Neuroscience, University of Fribourg, Fribourg, Switzerland.
J Neural Eng. 2018 Apr;15(2):026024. doi: 10.1088/1741-2552/aaa87a.
We recently developed soft neural interfaces enabling the delivery of electrical and chemical stimulation to the spinal cord. These stimulations restored locomotion in animal models of paralysis. Soft interfaces can be placed either below or above the dura mater. Theoretically, the subdural location combines many advantages, including increased selectivity of electrical stimulation, lower stimulation thresholds, and targeted chemical stimulation through local drug delivery. However, these advantages have not been documented, nor have their functional impact been studied in silico or in a relevant animal model of neurological disorders using a multimodal neural interface.
We characterized the recruitment properties of subdural interfaces using a realistic computational model of the rat spinal cord that included explicit representation of the spinal roots. We then validated and complemented computer simulations with electrophysiological experiments in rats. We additionally performed behavioral experiments in rats that received a lateral spinal cord hemisection and were implanted with a soft interface.
In silico and in vivo experiments showed that the subdural location decreased stimulation thresholds compared to the epidural location while retaining high specificity. This feature reduces power consumption and risks of long-term damage in the tissues, thus increasing the clinical safety profile of this approach. The hemisection induced a transient paralysis of the leg ipsilateral to the injury. During this period, the delivery of electrical stimulation restricted to the injured side combined with local chemical modulation enabled coordinated locomotor movements of the paralyzed leg without affecting the non-impaired leg in all tested rats. Electrode properties remained stable over time, while anatomical examinations revealed excellent bio-integration properties.
Soft neural interfaces inserted subdurally provide the opportunity to deliver electrical and chemical neuromodulation therapies using a single, bio-compatible and mechanically compliant device that effectively alleviates locomotor deficits after spinal cord injury.
我们最近开发了软神经接口，能够向脊髓提供电刺激和化学刺激。这些刺激恢复了瘫痪动物模型的运动能力。软接口可以放在硬脑膜下方或上方。理论上，硬膜下位置结合了许多优点，包括电刺激的选择性增加、更低的刺激阈值，以及通过局部药物输送进行靶向化学刺激。然而，这些优势尚未得到证实，也没有在使用多模态神经接口的神经紊乱的相关动物模型中通过计算机模拟或实验来研究它们的功能影响。
我们使用包括脊髓根的明确表示的大鼠脊髓的现实计算模型来描述硬膜下接口的募集特性。然后，我们在大鼠中进行了电生理实验来验证和补充计算机模拟。我们还在接受脊髓侧半切和软接口植入的大鼠中进行了行为实验。
计算机模拟和体内实验表明，与硬膜外位置相比，硬膜下位置降低了刺激阈值，同时保持了高度的特异性。这一特性降低了功耗和组织长期损伤的风险，从而提高了这种方法的临床安全性。半切导致对侧腿部的暂时性瘫痪。在此期间，仅对损伤侧进行电刺激的传递结合局部化学调节可使瘫痪腿部协调运动，而不影响所有测试大鼠中未受损的腿部。电极性能随时间保持稳定，而解剖检查显示出出色的生物整合特性。
硬膜下插入的软神经接口提供了使用单个生物兼容和机械顺应性装置进行电刺激和化学神经调节治疗的机会，该装置可有效缓解脊髓损伤后的运动功能障碍。
