A neuronal architecture underlying autonomic dysreflexia

Jan Elaine Soriano^#^{1

2

3

4

5}, Remi Hudelle^#^{4

5}, Lois Mahe^{4

5

6}, Matthieu Gautier^{4

5

6}, Alan Yue Yang Teo^{4

5}, Michael A Skinnider⁷, Achilleas Laskaratos^{4

5}, Steven Ceto^{4

5}, Claudia Kathe^{4

5

8}, Thomas Hutson⁹, Rebecca Charbonneau¹, Fady Girgis¹, Steve Casha¹, Julien Rimok^{1

2

3

10}, Marcus Tso^{1

2

3

10}, Kelly Larkin-Kaiser^{1

2

3

10}, Nicolas Hankov^{4

5}, Aasta Gandhi^{4

5}, Suje Amir^{4

5}, Xiaoyang Kang¹¹, Yashwanth Vyza^{5

12}, Eduardo Martin-Moraud^{4

5}, Stephanie Lacour^{5

12}, Robin Demesmaeker^{4

5}, Leonie Asboth^{4

5}, Quentin Barraud^{4

5}, Mark A Anderson^{4

5

8}, Jocelyne Bloch^{4

5

6

13}, Jordan W Squair^{14

15

16

17}, Aaron A Phillips^{18

19

20

21}, Gregoire Courtine^{22

23

24

25}

Affiliations

¹ Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
³ Restore Network, Hotchkiss Brain Institute, Libin Cardiovascular Institute, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁴ Defitech Center for Interventional Neurotherapies (.NeuroRestore), CHUV/UNIL/EPFL, Lausanne, Switzerland.
⁵ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
⁶ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
⁷ Lewis-Sigler Institute of Integrative Genomics and Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
⁸ Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁹ Wyss Center for Bio and Neuroengineering, Geneva, Switzerland.
¹⁰ Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹¹ Institute of Science and Technology Brain-inspired Intelligence, Fudan University, Shanghai, China.
¹² Laboratory for Soft Bioelectronic Interfaces (LSBI), NeuroX Institute, EPFL, Lausanne, Switzerland.
¹³ Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
¹⁴ Defitech Center for Interventional Neurotherapies (.NeuroRestore), CHUV/UNIL/EPFL, Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁵ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁶ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁷ Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁸ Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
¹⁹ Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
²⁰ Restore Network, Hotchkiss Brain Institute, Libin Cardiovascular Institute, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
²¹ Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
²² Defitech Center for Interventional Neurotherapies (.NeuroRestore), CHUV/UNIL/EPFL, Lausanne, Switzerland. gregoire.courtine@epfl.ch.
²³ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. gregoire.courtine@epfl.ch.
²⁴ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. gregoire.courtine@epfl.ch.
²⁵ Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. gregoire.courtine@epfl.ch.

^# Contributed equally.

PMID: 40963010
DOI: 10.1038/s41586-025-09487-w

A neuronal architecture underlying autonomic dysreflexia

Jan Elaine Soriano et al. Nature. 2025.

. 2025 Sep 17.

doi: 10.1038/s41586-025-09487-w. Online ahead of print.

Authors

Affiliations

¹ Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
³ Restore Network, Hotchkiss Brain Institute, Libin Cardiovascular Institute, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁴ Defitech Center for Interventional Neurotherapies (.NeuroRestore), CHUV/UNIL/EPFL, Lausanne, Switzerland.
⁵ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
⁶ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
⁷ Lewis-Sigler Institute of Integrative Genomics and Ludwig Institute for Cancer Research, Princeton University, Princeton, NJ, USA.
⁸ Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁹ Wyss Center for Bio and Neuroengineering, Geneva, Switzerland.
¹⁰ Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹¹ Institute of Science and Technology Brain-inspired Intelligence, Fudan University, Shanghai, China.
¹² Laboratory for Soft Bioelectronic Interfaces (LSBI), NeuroX Institute, EPFL, Lausanne, Switzerland.
¹³ Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
¹⁴ Defitech Center for Interventional Neurotherapies (.NeuroRestore), CHUV/UNIL/EPFL, Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁵ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁶ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁷ Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. jordan.squair@epfl.ch.
¹⁸ Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
¹⁹ Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
²⁰ Restore Network, Hotchkiss Brain Institute, Libin Cardiovascular Institute, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
²¹ Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. aaron.phillips@ucalgary.ca.
²² Defitech Center for Interventional Neurotherapies (.NeuroRestore), CHUV/UNIL/EPFL, Lausanne, Switzerland. gregoire.courtine@epfl.ch.
²³ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland. gregoire.courtine@epfl.ch.
²⁴ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. gregoire.courtine@epfl.ch.
²⁵ Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. gregoire.courtine@epfl.ch.

^# Contributed equally.

PMID: 40963010
DOI: 10.1038/s41586-025-09487-w

Abstract

Autonomic dysreflexia is a life-threatening medical condition characterized by episodes of uncontrolled hypertension that occur in response to sensory stimuli after spinal cord injury (SCI)¹. The fragmented understanding of the mechanisms underlying autonomic dysreflexia hampers the development of therapeutic strategies to manage this condition, leaving people with SCI at daily risk of heart attack and stroke^2-5. Here we expose the neuronal architecture that develops after SCI and causes autonomic dysreflexia. In parallel, we uncover a competing, yet overlapping neuronal architecture activated by epidural electrical stimulation of the spinal cord that safely regulates blood pressure after SCI. The discovery that these adversarial neuronal architectures converge onto a single neuronal subpopulation provided a blueprint for the design of a mechanism-based intervention that reversed autonomic dysreflexia in mice, rats and humans with SCI. These results establish a path towards essential pivotal device clinical trials that will establish the safety and efficacy of epidural electrical stimulation for the effective treatment of autonomic dysreflexia in people with SCI.

PubMed Disclaimer

Conflict of interest statement

Competing interests: G.C., A.A.P., J.W.S., J.B., R.D. and S.L. hold various patents in relation to the present work. G.C., A.A.P. and R.D. are consultants of ONWARD Medical. G.C., A.A.P., J.W.S., J.B. and S.L. are minority shareholders of ONWARD, a company with direct relationships with the presented work. The other authors declare no competing interests.

References

1. Phillips, A. A. & Krassioukov, A. V. Contemporary cardiovascular concerns after spinal cord injury: mechanisms, maladaptations, and management. J. Neurotrauma 32, 1927–1942 (2015). - PubMed - DOI
1. Squair, J. W., Phillips, A. A., Harmon, M. & Krassioukov, A. V. Emergency management of autonomic dysreflexia with neurologic complications. Can. Med. Assoc. J. 188, 1100–1103 (2016). - DOI
1. Wan, D. & Krassioukov, A. V. Life-threatening outcomes associated with autonomic dysreflexia: a clinical review. J. Spinal Cord Med. 37, 2–10 (2014). - PubMed - PMC - DOI
1. Cragg, J. J., Noonan, V. K., Krassioukov, A. & Borisoff, J. Cardiovascular disease and spinal cord injury: results from a national population health survey. Neurology 81, 723–728 (2013). - PubMed - PMC - DOI
1. Wu, J.-C. et al. Increased risk of stroke after spinal cord injury: a nationwide 4-year follow-up cohort study. Neurology 78, 1051–1057 (2012). - PubMed - DOI

LinkOut - more resources

Full Text Sources
- Nature Publishing Group

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

A neuronal architecture underlying autonomic dysreflexia

Affiliations

A neuronal architecture underlying autonomic dysreflexia

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources