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
Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Nature. 2025 Sep 17. doi: 10.1038/s41586-025-09487-w.
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). 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. 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.
自主神经反射异常是一种危及生命的医学状况，其特征是脊髓损伤（SCI）后因感觉刺激而出现无法控制的高血压发作。对自主神经反射异常潜在机制的碎片化理解阻碍了治疗该病症的治疗策略的发展，使脊髓损伤患者每天都面临心脏病发作和中风的风险。在这里，我们揭示了脊髓损伤后发展并导致自主神经反射异常的神经元结构。同时，我们发现了一种由脊髓硬膜外电刺激激活的相互竞争但又重叠的神经元结构，该结构在脊髓损伤后能安全地调节血压。这些对抗性神经元结构汇聚到单个神经元亚群的发现为设计基于机制的干预措施提供了蓝图，该干预措施可逆转小鼠、大鼠和人类脊髓损伤后的自主神经反射异常。这些结果为关键的器械临床试验奠定了基础，该试验将确定硬膜外电刺激有效治疗脊髓损伤患者自主神经反射异常的安全性和有效性。
