Prognostic Association between Changes in Low Molecular Weight Thiols and Small Vessel Burden in Acute Ischemic Stroke Following Thrombolysis

We aimed to explore the dynamic changes of low-molecular-weight thiols (LMWTs), especially reduced glutathione (rGSH), following intravenous thrombolysis in patients with acute ischemic stroke (AIS), as well as the relationships of rGSH dynamic changes and cerebral small vessel disease (CSVD) burden with 90-days functional outcomes. This study included 150 AIS patients undergoing intravenous thrombolysis. Plasma sample collection was completed before (T0) and at 24 h (T1) and 7 days (T2) after thrombolysis, followed by determination of total glutathione (tGSH), rGSH, total cystine (tCys), total homocysteine (tHcy) and glutathione/oxidized glutathione (GSH/GSSG) ratio. The dynamic change trend of LMWTs was assessed through repeated measures analysis of variance, and associations were analyzed using regression models. The rGSH level rose significantly within 7 days after thrombolysis (P < 0.001). tHcy declined significantly at T1 (P = 0.002) and remained at low levels. The CSVD total score [odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.22–2.36, P = 0.002] and 24-h rGSH change rate (for each 10% decrease, OR = 1.29, 95% CI = 1.07–1.55, P = 0.007) were independent predictors of poor outcome. CSVD burden significantly moderated the relationship between rGSH and outcome (P for interaction = 0.028). An elevation in rGSH in the early stage suggests the recovery of antioxidant defense, while an insufficient increase indicates persistent oxidative stress and limited antioxidant compensation. CSVD burden is capable of significantly enhancing the relationship between rGSH changes and functional outcomes. The combination of rGSH dynamic changes with CSVD burden assessment is a promising biomarker of stroke outcomes.