Nature · 2025
A neuronal architecture underlying autonomic dysreflexia.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Soriano Jan Elaine, Hudelle Remi, Mahe Lois, Gautier Matthieu, Teo Alan Yue Yang, Skinnider Michael A, Laskaratos Achilleas, Ceto Steven, Kathe Claudia, Hutson Thomas, Charbonneau Rebecca, Girgis Fady, Casha Steve, Rimok Julien, Tso Marcus, Larkin-Kaiser Kelly, Hankov Nicolas, Gandhi Aasta, Amir Suje, Kang Xiaoyang, Vyza Yashwanth, Martin-Moraud Eduardo, Lacour Stephanie, Demesmaeker Robin, Asboth Leonie, Barraud Quentin, Anderson Mark A, Bloch Jocelyne, Squair Jordan W, Phillips Aaron A, Courtine Gregoire
Аннотация
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 stroke2-5. 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.