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Peer-reviewedCC BY-NCJournal of stroke

Precision Oxygen Modulation in the Reperfusion Era: Conditioning and Therapeutic Strategies in Ischemic Stroke.

  • Weilin Liu1,2
  • Zihan Li1,3
  • Zhou Sun3
  • Jia Liu4
  • Xunming Ji5,6
6 affiliations
  1. 1Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Ministry of Science and Technology, Chinese Institutes for Medical Research, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
  2. 2Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
  3. 3School of Basic Medical Sciences, Capital Medical University, Beijing, China.
  4. 4Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Ministry of Science and Technology, Chinese Institutes for Medical Research, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. [email protected].
  5. 5Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Hypoxia Conditioning Translational Laboratory of Clinical Medicine, Ministry of Science and Technology, Chinese Institutes for Medical Research, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. [email protected].
  6. 6Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. [email protected].
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Abstract

Endovascular thrombectomy (EVT) and advanced perfusion imaging have transformed acute ischemic stroke (AIS) treatment, yet tissue hypoxia may persist because of delayed presentation, incomplete reperfusion, microvascular no-reflow, and secondary injury. Oxygen is an essential substrate for cerebral metabolism and a modifiable therapeutic exposure; however, clinical studies of oxygen-based interventions have yielded inconsistent results because of heterogeneity in timing, dose, delivery, and patient selection. Here we propose precision oxygen modulation (POM) as a stage-, phenotype-, and tissue-informed framework for the reperfusion era-treating oxygen exposure as a dose-titrated therapy that must be matched to the right patient, time window, physiological target, and safety boundary. POM integrates oxygen conditioning strategies that may prime neurovascular resilience before or around ischemia, time-limited therapeutic oxygen strategies deployed around reperfusion to support tissue at risk, and recovery-stage strategies paired with rehabilitation. We synthesize clinical and preclinical evidence linking oxygen tension to excitotoxicity, oxidative stress, inflammation, endothelial dysfunction, blood-brain barrier (BBB) integrity, and repair, while emphasizing the context-dependent risks of hyperoxia. We outline an operational decision framework and translational roadmap based on phenotype- and imaging-guided selection, biomarker validation, protocolized dosing, predefined safety boundaries, and phenotype-enriched randomized trials. POM is presented as a testable translational framework for organizing heterogeneous evidence and guiding the prospective validation of stage-specific oxygen modulation in modern stroke care.

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Cite

BibTeXRIS
BibTeX
@article{liu2026precision,
  title = {{Precision Oxygen Modulation in the Reperfusion Era: Conditioning and Therapeutic Strategies in Ischemic Stroke.}},
  author = {Weilin Liu and Zihan Li and Zhou Sun and Jia Liu and Xunming Ji},
  journal = {Journal of stroke},
  year = {2026},
  month = sep,
  doi = {10.5853/jos.2026.02747},
  url = {https://europepmc.org/article/MED/42894448},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Precision Oxygen Modulation in the Reperfusion Era: Conditioning and Therapeutic Strategies in Ischemic Stroke.
AU  - Weilin Liu
AU  - Zihan Li
AU  - Zhou Sun
AU  - Jia Liu
AU  - Xunming Ji
PY  - 2026
DA  - 2026/09/30
JO  - Journal of stroke
DO  - 10.5853/jos.2026.02747
UR  - https://europepmc.org/article/MED/42894448
AB  - Endovascular thrombectomy (EVT) and advanced perfusion imaging have transformed acute ischemic stroke (AIS) treatment, yet tissue hypoxia may persist because of delayed presentation, incomplete reperfusion, microvascular no-reflow, and secondary injury. Oxygen is an essential substrate for cerebral metabolism and a modifiable therapeutic exposure; however, clinical studies of oxygen-based interventions have yielded inconsistent results because of heterogeneity in timing, dose, delivery, and patient selection. Here we propose precision oxygen modulation (POM) as a stage-, phenotype-, and tissue-informed framework for the reperfusion era-treating oxygen exposure as a dose-titrated therapy that must be matched to the right patient, time window, physiological target, and safety boundary. POM integrates oxygen conditioning strategies that may prime neurovascular resilience before or around ischemia, time-limited therapeutic oxygen strategies deployed around reperfusion to support tissue at risk, and recovery-stage strategies paired with rehabilitation. We synthesize clinical and preclinical evidence linking oxygen tension to excitotoxicity, oxidative stress, inflammation, endothelial dysfunction, blood-brain barrier (BBB) integrity, and repair, while emphasizing the context-dependent risks of hyperoxia. We outline an operational decision framework and translational roadmap based on phenotype- and imaging-guided selection, biomarker validation, protocolized dosing, predefined safety boundaries, and phenotype-enriched randomized trials. POM is presented as a testable translational framework for organizing heterogeneous evidence and guiding the prospective validation of stage-specific oxygen modulation in modern stroke care.
SN  - 2287-6391
SN  - 2287-6405
ER  -