A neuronal architecture underlying autonomic dysreflexia
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)<sup>1</sup>. 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<sup>2-5</sup>. 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.
Authors
- Matthieu Gautier (ORCID: https://orcid.org/0000-0003-4910-8576)
- Suje Amir
- Jocelyne Bloch (ORCID: https://orcid.org/0000-0002-6405-1590)
- Robin Demesmaeker (ORCID: https://orcid.org/0000-0003-0856-0929)
- Stéphanie P. Lacour (ORCID: https://orcid.org/0000-0001-9075-4022)
- Grégoire Courtine (ORCID: https://orcid.org/0000-0002-5744-4142)
- Jan Elaine Soriano (ORCID: https://orcid.org/0000-0001-5553-0808)
- Loïs Mahe
- Kelly A. Larkin-Kaiser (ORCID: https://orcid.org/0000-0001-6205-0212)
- Aaron A. Phillips (ORCID: https://orcid.org/0000-0002-7845-1464)
- Nicolas Hankov (ORCID: https://orcid.org/0000-0001-7112-0091)
- Jordan W. Squair (ORCID: https://orcid.org/0000-0003-0551-859X)
- Quentin Barraud (ORCID: https://orcid.org/0000-0003-0894-1959)
- Thomas H. Hutson (ORCID: https://orcid.org/0000-0001-6795-2688)
- Claudia Kathe (ORCID: https://orcid.org/0000-0001-6441-1755)
- Michael A. Skinnider (ORCID: https://orcid.org/0000-0002-2168-1621)
- Xiaoyang Kang (ORCID: https://orcid.org/0000-0003-4372-9531)
- Yashwanth Vyza
- Fady Girgis
- Aasta P. Gandhi (ORCID: https://orcid.org/0000-0002-6206-6860)
- Achilleas Laskaratos (ORCID: https://orcid.org/0000-0002-2456-5781)
- Rémi Hudelle
- Steve Casha
- Eduardo Martin Moraud (ORCID: https://orcid.org/0000-0002-6148-7065)
- Mark A. Anderson (ORCID: https://orcid.org/0000-0003-1855-6106)
- Steven Ceto (ORCID: https://orcid.org/0000-0002-0101-3685)
- Léonie Asboth (ORCID: https://orcid.org/0000-0003-2414-9574)
- Rebecca Charbonneau (ORCID: https://orcid.org/0009-0006-6145-071X)
- Alan Yue Yang Teo (ORCID: https://orcid.org/0000-0002-3276-131X)
- Marcus Tso (ORCID: https://orcid.org/0000-0001-9094-1485)
- Julien Rimok
Institutions
- University of Calgary (CA)
- Princeton University (US)
- Fudan University (CN)
- Centre Hospitalier Universitaire Vaudois (CH)
- Shanghai Institute for Science of Science (CN)
- Alberta Bone and Joint Health Institute (CA)
- Ludwig Cancer Research (US)
- Wyss Center for Bio and Neuroengineering (CH)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- Hotchkiss Brain Institute (CA)
- École Polytechnique Fédérale de Lausanne (CH)
- Libin Cardiovascular Institute of Alberta (CA)
- University of Lausanne (CH)
Publication Details
- Journal
- Nature
- Published
- 2025-09-17
- DOI
- https://doi.org/10.1038/s41586-025-09487-w
- Citations
- 2
- Primary Topic
- Spinal Cord Injury Research
- Type
- article
- Field-Weighted Citation Impact
- 2.94