Nitric oxide-related brain damage in acute ischemic stroke.
OBJECTIVE
The neurotoxic and neuroprotective role of nitric oxide (NO) in experimental cerebral ischemia has generated considerable debate. The aim of this study was to analyze the relationship between NO metabolite (NO-m) concentrations in cerebrospinal fluid (CSF) and clinical and neuroimaging parameters of brain injury in patients with acute ischemic stroke.


METHODS
We studied 102 patients and 24 control subjects who were included in a larger previous study conducted to analyze risk factors of progressing stroke. NO generation was calculated by quantifying nitrates and nitrites with 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 48 hours after inclusion. Infarct volume was measured on days 4 to 7 by cranial CT.


RESULTS
Median NO-m concentrations [quartiles] were 2.1 [1.0, 4.5] micromol/mL in patients and 1.0 [1.0, 1.0] micromol/mL in control subjects (P<0.0001). In 45 patients with subsequent early neurological deterioration, NO-m levels 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] micromol/mL, P<0.0001). There was a moderate correlation between NO-m and infarct volume (coefficient 0.39, P<0. 001). NO-m concentrations >5.0 micromol/mL were significantly associated with early neurological worsening (OR 5.7, 95% CI 1.2 to 27.4; P=0.030) independent of other important factors related to progressing stroke, such as CSF glutamate levels.


CONCLUSIONS
Our clinical findings suggest an important role of NO generation in acute ischemic stroke. Increased NO-m in CSF are associated with a greater brain injury and early neurological deterioration.
Castillo
J
J
Department of Neurology, Complejo Hospitalario Universitario, Santiago de Compostela, Spain.
Rama
R
R
Dávalos
A
A
D000208:Acute Disease; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging; D001925:Brain Damage, Chronic / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009420:Nervous System / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D020521:Stroke / Q000150:complications* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed
D009569:Nitric Oxide