Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury

Jordan W. Squair, Matthieu Gautier, Lois Mahe, Jan Elaine Soriano, Andreas Rowald, Arnaud Bichat, Newton Cho, Mark A. Anderson, Nicholas D. James, Jerome Gandar, Anthony V. Incognito, Giuseppe Schiavone, Zoe K. 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, Rik Buschman, Nicolas Buse, Tim Denison, Sean Dukelow, Rebecca Charbonneau, Ian Rigby, Steven K. Boyd, Philip J. Millar, Eduardo Martin Moraud, Marco Capogrosso, Fabien B. Wagner, Quentin Barraud, Erwan Bezard, Stéphanie P. Lacour, Jocelyne Bloch, Grégoire Courtine () and Aaron A. Phillips ()
Additional contact information
Jordan W. Squair: Swiss Federal Institute of Technology (EPFL)
Matthieu Gautier: Swiss Federal Institute of Technology (EPFL)
Lois Mahe: Swiss Federal Institute of Technology (EPFL)
Jan Elaine Soriano: University of Calgary
Andreas Rowald: Swiss Federal Institute of Technology (EPFL)
Arnaud Bichat: Swiss Federal Institute of Technology (EPFL)
Newton Cho: Swiss Federal Institute of Technology (EPFL)
Mark A. Anderson: Swiss Federal Institute of Technology (EPFL)
Nicholas D. James: Swiss Federal Institute of Technology (EPFL)
Jerome Gandar: Swiss Federal Institute of Technology (EPFL)
Anthony V. Incognito: University of Calgary
Giuseppe Schiavone: Swiss Federal Institute of Technology (EPFL)
Zoe K. Sarafis: Swiss Federal Institute of Technology (EPFL)
Achilleas Laskaratos: Swiss Federal Institute of Technology (EPFL)
Kay Bartholdi: Swiss Federal Institute of Technology (EPFL)
Robin Demesmaeker: Swiss Federal Institute of Technology (EPFL)
Salif Komi: Swiss Federal Institute of Technology (EPFL)
Charlotte Moerman: Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Bita Vaseghi: University of Calgary
Berkeley Scott: University of Calgary
Ryan Rosentreter: University of Calgary
Claudia Kathe: Swiss Federal Institute of Technology (EPFL)
Jimmy Ravier: Swiss Federal Institute of Technology (EPFL)
Laura McCracken: Swiss Federal Institute of Technology (EPFL)
Xiaoyang Kang: Swiss Federal Institute of Technology (EPFL)
Nicolas Vachicouras: Swiss Federal Institute of Technology (EPFL)
Florian Fallegger: Swiss Federal Institute of Technology (EPFL)
Ileana Jelescu: Swiss Federal Institute of Technology (EPFL)
YunLong Cheng: Motac Neuroscience Ltd
Qin Li: Motac Neuroscience Ltd
Rik Buschman: Medtronic
Nicolas Buse: Medtronic
Tim Denison: University of Oxford
Sean Dukelow: University of Calgary
Rebecca Charbonneau: University of Calgary
Ian Rigby: University of Calgary, Calgary
Steven K. Boyd: University of Calgary
Philip J. Millar: University of Guelph
Eduardo Martin Moraud: Lausanne University Hospital (CHUV) and University of Lausanne (UNIL)
Marco Capogrosso: University of Fribourg
Fabien B. Wagner: Swiss Federal Institute of Technology (EPFL)
Quentin Barraud: Swiss Federal Institute of Technology (EPFL)
Erwan Bezard: Motac Neuroscience Ltd
Stéphanie P. Lacour: Swiss Federal Institute of Technology (EPFL)
Jocelyne Bloch: Swiss Federal Institute of Technology (EPFL)
Grégoire Courtine: Swiss Federal Institute of Technology (EPFL)
Aaron A. Phillips: University of Calgary

Nature, 2021, vol. 590, issue 7845, 308-314

Abstract: Abstract Spinal cord injury (SCI) induces haemodynamic instability that threatens survival1–3, 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.

Date: 2021
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DOI: 10.1038/s41586-020-03180-w

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