Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke

Abstract

Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive and independent associations to outcome. Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month. Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most of these correlations disappeared by 72 poststroke hours. Correlation of MCP-1 with both ADMA and SDMA levels at 6 hours was associated with both NIHSS worsening and poststroke infections, respectively; sCD40L and SDMA correlation at 6 hours was also associated with NIHSS worsening. Negative correlation between P-selectin and L-arginine concentrations in the hyperacute phase was associated with NIHSS worsening. Strong negative correlation was found between IL-6 and L-arginine levels in the hyperacute phase in patients with poststroke infection. Only L-arginine and SDMA at 72 hours were independently associated with poststroke infection respectively. Concentration of L-arginine and ADMA/SDMA differentially correlates with thrombo-inflammation in the hyperacute phase of ischemic stroke. Such correlations are independently associated with poststroke infection but not with other outcomes.