Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury
Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury
复制标题
DOI：
10.1038/s41586-020-03180-w
复制
发表时间：
2021-01-27
期刊：
影响因子：
64.8
通讯作者：
Phillips, Aaron A.
中科院分区：
文献类型：
--
作者：
Squair, Jordan W.;Gautier, Matthieu;Phillips, Aaron A.
脊髓损伤（SCI）引起血液动力学不稳定，威胁生存（1-3），损害神经恢复（4，5），增加心血管疾病的风险（6，7），并降低生活质量（8，9）。在这种情况下，血液动力学不稳定是由于对位于脊髓中的交感神经回路的脊髓上传出命令的中断（10），这阻止了自然压力反射控制这些回路以调节外周血管阻力。脊髓的硬膜外电刺激（EES）已被证明可以补偿损伤下方运动回路的脊髓上命令中断（11），并恢复瘫痪后的行走（12）。在这里，我们利用这些概念来开发EES方案，以恢复SCI后的血液动力学稳定性。我们建立了一个临床前模型，使我们能够解剖交感神经回路的拓扑结构和动力学，并了解EES如何参与这些回路。我们将这些空间和时间的功能纳入刺激协议，设想一个临床级的仿生血液动力学调节器，在一个闭环中运行。在急性和慢性SCI后，这种“神经假体压力反射”在啮齿动物、非人类灵长类动物和人类中长时间控制血液动力学。我们现在将进行临床试验，将神经假体压力感受器反射变成SCI患者的常用疗法。
Spinal cord injury (SCI) induces haemodynamic instability that threatens survival(1-3), impairs neurological recovery(4,5), increases the risk of cardiovascular disease(6,7), and reduces quality of life(8,9). Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord(10), 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(11), and restored walking after paralysis(12). 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.