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, Aaron A. Phillips
Nature. 2021-01-27; 590(7845): 308-314
DOI: 10.1038/s41586-020-03180-w

https://www.bordeaux-neurocampus.fr/11995

1. Nature. 2021 Feb;590(7845):308-314. doi: 10.1038/s41586-020-03180-w. Epub 2021
Jan 27.

Squair JW(1)(2)(3)(4)(5)(6)(7)(8)(9)(10), Gautier M(#)(1)(4), Mahe L(#)(1)(4),
Soriano JE(#)(5)(6)(7)(10), Rowald A(#)(1)(4), Bichat A(1)(4), Cho N(1)(4)(11),
Anderson MA(1)(4), James ND(1)(4), Gandar J(1)(4), Incognito AV(10)(12),
Schiavone G(13), Sarafis ZK(1)(4), Laskaratos A(1)(4), Bartholdi K(1)(4),
Demesmaeker R(1)(4), Komi S(1)(4), Moerman C(3)(4), Vaseghi B(5)(6)(7), Scott
B(5)(6)(7)(10), Rosentreter R(5)(6)(7)(10), Kathe C(1)(4), Ravier J(1)(4),
McCracken L(1)(4), Kang X(13), Vachicouras N(13), Fallegger F(13), Jelescu
I(14), Cheng Y(15), Li Q(15), Buschman R(16), Buse N(16), Denison T(17)(18),
Dukelow S(5)(6)(7)(10)(19), Charbonneau R(6)(10), Rigby I(20), Boyd SK(19),
Millar PJ(12), Moraud EM(3)(4), Capogrosso M(21), Wagner FB(1)(4)(22), Barraud
Q(1)(4), Bezard E(15)(22)(23), Lacour SP(13), Bloch J(1)(2)(3)(4), Courtine
G(24)(25)(26)(27), Phillips AA(28)(29)(30)(31)(32).

Author information:
(1)Center for Neuroprosthetics and Brain Mind Institute, School of Life
Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
(2)Department of Neurosurgery, Lausanne University Hospital (CHUV) and
University of Lausanne (UNIL), Lausanne, Switzerland.
(3)Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and
University of Lausanne (UNIL), Lausanne, Switzerland.
(4)Defitech Center for Interventional Neurotherapies (.NeuroRestore),
CHUV/UNIL/EPFL, Lausanne, Switzerland.
(5)Department of Physiology and Pharmacology, Cumming School of Medicine,
University of Calgary, Calgary, Alberta, Canada.
(6)Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming
School of Medicine, University of Calgary, Calgary, Alberta, Canada.
(7)Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming
School of Medicine, University of Calgary, Calgary, Alberta, Canada.
(8)MD/PhD Training Program, Faculty of Medicine, University of British Columbia,
Vancouver, British Columbia, Canada.
(9)International Collaboration on Repair Discoveries (ICORD), University of
British Columbia, Vancouver, British Columbia, Canada.
(10)RestoreNetwork, Hotchkiss Brain Institute, Libin Cardiovascular Institute,
McCaig Institute for Bone and Joint Health, Cumming School of Medicine,
University of Calgary, Calgary, Alberta, Canada.
(11)Department of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.
(12)Department of Human Health and Nutritional Sciences, University of Guelph,
Guelph, Ontario, Canada.
(13)Centre for Neuroprosthetics, Institute of Microengineering, Swiss Federal
Institute of Technology (EPFL), Lausanne, Switzerland.
(14)Center for Biomedical Imaging, Swiss Federal Institute of Technology (EPFL),
Lausanne, Switzerland.
(15)Motac Neuroscience Ltd, Manchester, UK.
(16)Medtronic, Minneapolis, MN, USA.
(17)Department of Engineering Science and Clinical Neurosciences, University of
Oxford, Oxford, UK.
(18)Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
(19)Department of Radiology, McCaig Institute for Bone and Joint Health,
University of Calgary, Calgary, Alberta, Canada.
(20)Department of Emergency Medicine, Cumming School of Medicine, University of
Calgary, Calgary, Alberta, Canada.
(21)Faculty of Biology, University of Fribourg, Fribourg, Switzerland.
(22)Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR, 5293,
Bordeaux, France.
(23)Institut des Maladies Neurodégénératives, CNRS, UMR, 5293, Bordeaux, France.
(24)Center for Neuroprosthetics and Brain Mind Institute, School of Life
Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
.
(25)Department of Neurosurgery, Lausanne University Hospital (CHUV) and
University of Lausanne (UNIL), Lausanne, Switzerland. .
(26)Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and
University of Lausanne (UNIL), Lausanne, Switzerland. .
(27)Defitech Center for Interventional Neurotherapies (.NeuroRestore),
CHUV/UNIL/EPFL, Lausanne, Switzerland. .
(28)Department of Physiology and Pharmacology, Cumming School of Medicine,
University of Calgary, Calgary, Alberta, Canada. .
(29)Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming
School of Medicine, University of Calgary, Calgary, Alberta, Canada.
.
(30)Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming
School of Medicine, University of Calgary, Calgary, Alberta, Canada.
.
(31)International Collaboration on Repair Discoveries (ICORD), University of
British Columbia, Vancouver, British Columbia, Canada.
.
(32)RestoreNetwork, Hotchkiss Brain Institute, Libin Cardiovascular Institute,
McCaig Institute for Bone and Joint Health, Cumming School of Medicine,
University of Calgary, Calgary, Alberta, Canada. .
(#)Contributed equally

Comment in
Nature. 2021 Feb;590(7845):223-224. doi: 10.1038/d41586-021-00087-y.
Nat Rev Neurosci. 2021 Apr;22(4):193. doi: 10.1038/s41583-021-00440-0.

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.