Work

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

Year: 2026

Type: review

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.

Source: Journal of Stroke

DOI: 10.5853/jos.2026.02747

Authors: Weilin Liu, Zihan Li, Zhou Sun, Jia Liu, Xunming Ji

Institutions: Capital Medical University, Xuan Wu Hospital of the Capital Medical University, Beijing Institute for Brain Disorders

Language: English

Topic: Acute Ischemic Stroke Management

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Natural Science Foundation of China, Capital Medical University, Beijing Municipal Natural Science Foundation