Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
Nature. 2021 Feb;590(7845):308-314. doi: 10.1038/s41586-020-03180-w. Epub 2021 Jan 27.
Spinal cord injury (SCI) induces haemodynamic instability that threatens survival, impairs neurological recovery, increases the risk of cardiovascular disease, and reduces quality of life. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury, and restored walking after paralysis. Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This 'neuroprosthetic baroreflex' controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI.
脊髓损伤 (SCI) 会导致血流动力学不稳定，威胁生命，损害神经恢复，增加心血管疾病风险，并降低生活质量。在这种情况下，血流动力学不稳定是由于脊髓中位于交感神经回路的上位传出命令中断，从而阻止自然压力反射来控制这些回路以调节外周血管阻力。脊髓电刺激 (EES) 已被证明可以补偿损伤以下运动回路中断的上位命令，并在瘫痪后恢复行走。在这里，我们利用这些概念开发了 EES 方案，以恢复 SCI 后的血流动力学稳定性。我们建立了一个临床前模型，使我们能够剖析交感神经回路的拓扑结构和动力学，并了解 EES 如何作用于这些回路。我们将这些空间和时间特征纳入刺激方案中，以设计一种临床级仿生血流动力学调节器，该调节器在急性和慢性 SCI 后，在啮齿动物、非人灵长类动物和人类中可以进行长时间的闭环控制。我们现在将进行临床试验，将神经假体压力反射转变为 SCI 患者常用的治疗方法。
