Blood–Brain Barrier Permeability Dynamics and Mediation of Triglyceride–Glucose Index on Acute Ischemic Stroke Outcomes

Background The evolution and severity of blood–brain barrier (BBB) permeability in the core and penumbra over time in acute ischemic stroke remain poorly understood. Recent studies have found that elevated triglyceride–glucose (TyG) index is associated with higher stroke recurrence, functional deterioration, and death. We investigated BBB permeability dynamics in patients with acute ischemic stroke and the impact of the BBB disruption–mediated TyG index on outcomes. Methods This double‐centric retrospective study included patients with acute anterior large‐artery occlusion from January 2019 to December 2023. BBB permeability was measured as flow extraction product (FED) values in the largest core and penumbra slices using computed tomography perfusion. The TyG index was calculated from triglyceride and glucose levels. Poor outcome was defined as a 90‐day modified Rankin Scale score of 3 to 6. Linear correlation evaluated relationships between FED values, time, and TyG index. Logistic regression analyzed associations between FED, TyG index, and outcomes. Mediation analysis assessed BBB disruption’s role in the insulin resistance–outcome relationship. Results This study included 274 patients (median age, 67 years [interquartile range, 57–74]; 179 men [66%]). Penumbra FED values increased with time ( r =0.143; P =0.022), and core FED values were higher than penumbra ( P <0.01). A higher TyG index was associated with poor outcomes (odds ratio, 6.6 [95% CI, 1.0–41.7]; P =0.04) and higher core FED values (odds ratio, 4.3 [95% CI, 1.4–12.9]; P =0.01). The highest TyG tertile had 9.96 and 17.51 times higher odds of increased core FED values ( P =0.004) and poor outcomes ( P =0.044). Mediation analysis indicated higher core FED values fully mediated the insulin resistance–outcome relationship ( P =0.041). Conclusions FED values were higher in the core and increased over time, contributing to worse outcomes. An elevated TyG index mediates worse outcomes through increased BBB permeability, highlighting BBB stabilization as a potential therapeutic target.