Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury

2021 · Jordan Squair, Matthieu Gautier, Lois Mahe, Jan Soriano, Arnaud Bichat, Newton Cho, Mark Anderson, Nicholas James, Jerome Gandar, Anthony Incognito V, Giuseppe Schiavone, Zoe Sarafis, Achilleas Laskaratos, Kay Bartholdi, Robin Demesmaeker, Salif Komi, Charlotte Moerman, Bita Vaseghi, Berkeley Scott, Ryan Rosentreter, Claudia Kathe, Jimmy Ravier, Laura McCracken, Xiaoyang Kang, Nicolas Vachicouras, Florian Fallegger, Ileana Jelescu, YunLong Cheng, Qin Li, Nicolas Buse, Tim Denison, Sean Dukelow, Rebecca Charbonneau, Ian Rigby, Steven Boyd, Philip Millar, Eduardo Moraud, Marco Capogrosso, Fabien Wagner, Quentin Barraud, Erwan Bezard, Stéphanie Lacour, Jocelyne Bloch, Grégoire Courtine, Aaron Phillips, A Abdelkader · Nature

Abstract

Abstract Spinal cord injury (SCI) induces haemodynamic instability that threatens survival1,2,3, impairs neurological recovery4,5, increases the risk of cardiovascular disease6,7, and reduces quality of life8,9. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord10, 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 injury11, and restored walking after paralysis12. 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.

Publication Details

Journal
Nature
Volume
590
Pages
308–314