Advantages of soft subdural implants for the delivery of electrochemical neuromodulation therapies to the spinal cord
Advantages of soft subdural implants for the delivery of electrochemical neuromodulation therapies to the spinal cord
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DOI：
10.1088/1741-2552/aaa87a
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发表时间：
2018-04-01
影响因子：
4
通讯作者：
Courtine, Gregoire
中科院分区：
文献类型：
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作者：
Capogrosso, Marco;Gandar, Jerome;Courtine, Gregoire
Objective.我们最近开发了软神经接口，能够将电刺激和化学刺激传递到脊髓。这些刺激恢复了瘫痪动物模型的运动能力。软接口可以放置在硬脑膜下方或上方。理论上，硬膜下定位结合了许多优点，包括增加电刺激的选择性、降低刺激阈值和通过局部药物递送的靶向化学刺激。然而，这些优点尚未被记录，也没有在计算机模拟或使用多模式神经接口的神经系统疾病的相关动物模型中研究其功能影响。Approach.我们的特点是招聘性质的硬膜下接口使用现实的计算模型，包括明确表示的脊髓根的大鼠脊髓。然后，我们验证和补充计算机模拟与大鼠的电生理实验。我们还在接受脊髓半切并植入软界面的大鼠中进行了行为实验。主要结果。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，同时保持了高特异性。该功能降低了功耗和组织长期损伤的风险，从而提高了该方法的临床安全性。半切术引起了同侧腿部的短暂瘫痪。在此期间，仅限于受伤侧的电刺激结合局部化学调节的递送使得所有测试大鼠的瘫痪腿能够协调自发运动，而不影响未受损的腿。电极性能随时间保持稳定，而解剖学检查显示出优异的生物整合性能。意义硬脑膜下插入的软神经接口提供了使用单个生物相容性和机械顺应性装置递送电和化学神经调节疗法的机会，该装置有效地消除脊髓损伤后的运动缺陷。
Objective. 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. Approach. 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. Main results. 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. Significance. 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.