Role of asymmetric dimethyl-arginine and NOX-2 in activation of leptomeningeal collaterals after acute ischemic stroke

Leptomeningeal collateral (LMC) circulation helps preserve brain tissue during acute ischemic stroke (AIS), with poor collateral status predicting worse outcomes. This study assessed the association between asymmetric dimethylarginine (ADMA), LMCs, infarct volume, and oxidative stress in 101 AIS patients with large vessel occlusion within 6h or wake-up stroke. LMC status was graded using the Menon score on CT angiography (categorized as poor, intermediate, or good), and recanalization was assessed by the modified Thrombolysis in Cerebral Infarction score. Serum ADMA and NOX2 levels were measured at admission (< 6h, T0), 24h (T1), and 48h (T2). Among patients, 43.1% had good, 35.3% intermediate, 21.6% poor LMC status. Higher admission ADMA levels were significantly associated with poor LMC (p = 0.028) and more severe neurological deficits at T1 and T2 (p = 0.005, p = 0.008). ADMA levels increased over time (p = 0.046), and correlated with NOX2 at T1 (p < 0.001). Rising NOX2 was associated with increased neutrophils (p = 0.013) and decreased lymphocytes (p = 0.006). ADMA likely impairs endothelial function by reducing nitric oxide availability and enhancing NOX2-driven oxidative stress. Statin use was associated with lower NOX2 levels. These findings support a role for the ADMA-NO-NOX2 axis in limiting collateral circulation. Targeting this axis may represent a therapeutic strategy to improve outcomes in AIS.