Optimal closed-loop feedback control of blood flow after spinal cord injury with norepinephrine
After spinal cord injury, clinical management aims to support tissue perfusion, but current methods rely on the indirect control of arterial blood pressure without direct measurement of the local blood flow. This limits the ability to tailor drug delivery to the injured tissue. Here, we show that spinal cord blood flow can be regulated using a closed-loop controller that adjusts vasopressor infusion on the basis of real-time ultrasound flow measurement. We characterize the dynamic relationship between drug infusion, arterial pressure and spinal cord blood flow, and we use these data to design a feedback controller that targets a predefined flow level. We validate the system in simulations, implement the controller in real time in rodents and translate it to pigs. We show that the controller reduced blood flow deviations and variability compared with constant dosing and supported functional recovery in a rodent survival model. These results show a closed-loop spinal cord perfusion control strategy that leverages clinically available measurements and pharmacological interventions, supporting its translation to clinical settings for the management of acute spinal cord injury.
Authors
- Kelly Jiang (ORCID: https://orcid.org/0000-0002-1144-7882)
- Meghana Bhimreddy (ORCID: https://orcid.org/0000-0001-7570-4094)
- Andrew M. Hersh (ORCID: https://orcid.org/0000-0003-1755-3974)
- A. Daniel Davidar (ORCID: https://orcid.org/0000-0002-1508-3449)
- Arjun Kumar Menta (ORCID: https://orcid.org/0000-0002-6371-6052)
- Kimberly Ashayeri (ORCID: https://orcid.org/0000-0002-3904-273X)
- Claire Hao (ORCID: https://orcid.org/0000-0002-5937-5777)
- Max Kerensky (ORCID: https://orcid.org/0009-0008-0138-8218)
- Nicholas Theodore (ORCID: https://orcid.org/0000-0001-5355-2683)
- Amir Manbachi (ORCID: https://orcid.org/0000-0003-0206-5230)
- Angelica F. Lopez (ORCID: https://orcid.org/0000-0002-4163-2915)
- Carly Weber-Levine (ORCID: https://orcid.org/0000-0003-2057-8419)
- Patrick J. Kramer (ORCID: https://orcid.org/0000-0003-0635-0629)
- Ritvik Jillala (ORCID: https://orcid.org/0000-0003-3061-7338)
- Sridevi V. Sarma (ORCID: https://orcid.org/0000-0002-4817-6625)
- Nitish V. Thakor (ORCID: https://orcid.org/0000-0002-9981-9395)
- Denis Routkevitch (ORCID: https://orcid.org/0000-0002-7144-6347)
- Nicholas Kats
- Emily C. Baca
- Zoe Soulé (ORCID: https://orcid.org/0009-0000-5901-4931)
- Vikas N. Vattipally (ORCID: https://orcid.org/0009-0000-6920-2311)
- Constantin Smit (ORCID: https://orcid.org/0000-0001-5259-7601)
- Ryan S. Bohluli (ORCID: https://orcid.org/0000-0003-4182-5773)
- Neil Arya Babu
- Ben Bykov
- Mitchell Pelline
- Noah Lu
- Patrick Myers
Institutions
- University of Nevada, Reno (US)
- Johns Hopkins University (US)
- University of Phoenix (US)
- University of Washington (US)
- University of Arizona College of Medicine- Phoenix (US)
- Phoenix College (US)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1038/s41551-026-01777-6
- Citations
- 1
- Primary Topic
- Spinal Cord Injury Research
- Type
- article
- Field-Weighted Citation Impact
- 4.57
Funders
- Johns Hopkins University
- National Institutes of Health
- Defense Advanced Research Projects Agency
- Advanced Research Projects Agency
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- National Center for Advancing Translational Sciences