Nitric oxide-related brain damage in acute ischemic stroke

Background and Purpose-The neurotoxic and neuroprotective role of nitric ox ide (NO) in experimental cerebral ischemia has generated considerable debat e. The aim of this study was to analyze the relationship between NO metabol ite (NO-m) concentrations in cerebrospinal fluid (CSF) and clinical and neu roimaging parameters of brain injury in patients with acute ischemic stroke . Methods-We studied 102 patients and 24 control subjects who were included i n a larger previous study conducted to analyze risk factors of progressing stroke. NO generation was calculated by quantifying nitrates and nitrites w ith a colorimetric assay in CSF samples obtained within the first 24 hours from symptoms onset. Early neurological deterioration was defined as a fall of 1 or more points in Canadian Stroke Scale score between admission and 4 8 hours after inclusion. Infarct volume was measured on days 4 to 7 by cran ial CT. Results-Median NO-m concentrations [quartiles] were 2.1 [1.0, 4.5] mu mol/m L in patients and 1.0 [1.0, 1.0] mu mol/mL in control subjects (P<0.0001). In 45 patients with subsequent early neurological deterioration, NO-m level s in CSF were significantly higher than in those with stable stroke (4.0 [1 .7, 7.8] versus in 1.6 [1.0, 2.5] mu mol/mL, P<0.0001). There was a moderat e correlation between NO-m and infarct volume (coefficient 0.39, P<0.001). NO-m concentrations >5.0 mu mol/mL were significantly associated with early neurological worsening (OR 5.7, 95% CI 1.2 to 27.4; P=0.030) independent o f other important factors related to progressing stroke, such as CSF glutam ate levels. Conclusions-Our clinical findings suggest an important: role of NO generati on in acute ischemic stroke. Increased NO-m in CSF are associated with a gr eater brain injury and early neurological deterioration.