In this exploratory, hypothesis-generating analysis of the INSPIRE trial, ischemic postconditioning after successful recanalization was associated with lower neutrophil activation, slower clot propagation, and faster microvascular transit, and multi-omics profiling pointed to blood-brain barrier integrity and mitochondrial bioenergetics as candidate pathways.
Patients receiving ischemic postconditioning (IPostC) had lower neutrophil CD11b expression in arterial blood drawn about 15 minutes after successful recanalization than controls.
IPostC was associated with a lower thromboelastography α-angle, indicating slower clot propagation.
IPostC was associated with shorter quantitative DSA-derived microcirculation time, indicating faster microvascular transit.
Longer microcirculation time correlated with greater infarct growth.
Plasma proteomic and metabolomic profiling identified signals involving blood-brain barrier and extracellular-matrix organization and mitochondrial bioenergetics.
Few omics signals survived false discovery rate correction.
The parent INSPIRE trial delivered IPostC in situ as four cycles of 2-minute balloon inflation and 2-minute deflation at the previously occluded arterial segment immediately after successful recanalization, and it reduced infarct growth from baseline to 48 h.
After a stroke caused by a blocked brain artery, doctors can remove the clot with a catheter, but reopening the vessel doesn't always restore blood flow in the tiny vessels of the brain. In the INSPIRE trial, a technique called ischemic postconditioning, in which a balloon is briefly inflated and deflated four times at the spot of the former blockage right after the clot is removed, reduced how much the stroke damage grew over 48 hours. This follow-up analysis examined blood and imaging measures to look for how it might work. Patients who received the technique had lower activation of neutrophils (an inflammatory white blood cell), slower clot-forming activity on a blood clotting test, and faster blood transit through small brain vessels on angiography. Slower transit through the small vessels was linked to larger growth of stroke damage. Protein and metabolite profiling in a smaller group of 29 patients hinted that the blood-brain barrier and the energy-producing machinery of cells (mitochondria) might be involved. These results are preliminary. The study was small, many comparisons were not corrected for chance findings, and in the omics analysis no proteins and only 17 metabolites held up after correction. This research suggests possible mechanisms worth testing, but larger studies are needed to confirm them.
Xu Y, Lu D, Liu S, Jiang X, Wang Q, Luo L, et al.. (2026). Immunothrombosis Biomarkers and Multi-Omics Profiles After Successful Recanalization in Patients Receiving Ischemic Postconditioning: An Exploratory Analysis of the INSPIRE Trial.. Translational stroke research. https://doi.org/10.1007/s12975-026-01513-x