PLASMA
LEVELS OF CHOLESTERYL ESTER
HYDROPEROXIDES CORRELATE WITH STROKE SEVERITY
AND SIZE OF THE INFARCT
M. C. Polidori, G.
Nelles, A. Cherubini, P. Mecocci, G. Rordorf, B. Frei,
W. J. Koroshetz, M. F. Beal, U. Senin
Institute of Gerontology and Geriatrics, Perugia University Hospital, Perugia,
Italy; Neurology Service, Massachusetts General Hospital and Harvard
Medical School, Boston, MA, USA; Whitaker Cardiovascular Institute,
Boston University, Boston, MA, USA
Introduction
Oxidation of cellular macromolecules and lipid peroxidation have
been implicated in the etiology of numerous disease states. In the central nervous system,
both stroke and neurotrauma have been proposed to initiate a sequence of oxidative events
which ultimately lead to neuronal cell death, while some of the antioxidant defenses of
the organism have been shown to be involved in the protection of the brain damage under
conditions of focal ischemia in animal models, but evidence in humans is limited.
Patients and Methods
Thirty-two patients with large artery cortical stroke (25M, 7F,
67.9(2.6 y), 13 neurologic controls with lacunar stroke (9M, 4F, 74.8(2.5 y) and 20 young
healthy subjects (10M, 10F, 30.7(4.3, normal controls) were studied. Using all available
clinical and neuroradiologic data, patients were classified according to the TOAST subtype
classification system and on the basis of the cerebral vascular territory involved. In
stroke patients, a sample of blood was obtained within 24 hrs from the stroke onset, then
every other day up to one week, for the measurement of plasma levels of lipid peroxides
– measured as cholesteryl ester hydroperoxides, CE-OOH, with a highly sensitive and
selective HPLC assay with chemiluminescence detection – and vitamin C (ascorbic acid,
AA). In control subjects, one single plasma sample was obtained for the assay of CE-OOH
and AA. In all patients, NIH stroke scale and Glasgow coma scale were administered on
admission and daily until discharge for the monitoring of the neurological deficit. In 20
patients who had adequate neuroimaging studies it was possible to determine the size of
the stroke volume by scanning the CT/MRI films obtained 48-72 h after the ictus into a
computer. The scanned images were stored on an optical disk and then exported into
NIH-image 1.52 software for measurement of stroke volumes. The scale on each slice was
used to adjust a given distance to the number of pixels in each individual case. Using the
free draw tool, the stroke area on each slice was captured by drawing along the border of
the stroke and the unaffected tissue. The area (mm2) was then multiplied with the slice
thickness. The volumes of each slice showing the stroke were finally added together to
compute the total infarct volume of each subject.
Results
Plasma CE-OOH were significantly higher in patients with cortical
stroke as compared with lacunar stroke at all time points studied (p<0.001). Among
patients with cortical stroke, those with larger arteries involved had significantly
higher CE-OOH plasma levels (p<0.005). CE-OOH were undetectable in 20 normal control
subjects. There were small, not significant decreases in plasma AA levels in cortical
compared to lacunar stroke patients on days 3 and 5 after the ictus. Nevertheless, AA and
CE-OOH levels in all patients were inversely related (r=0.29, p<0.01). There was a
significant negative correlation of the NIH stroke scale with AA levels (r=-0.17,
p<0.02), a significant positive correlation with CE-OOH levels (r=0.59, p<0.01).
Four patients who died with massive stroke had significantly higher levels of CE-OOH than
the patients who survived (p<0.02). Finally, in those 20 patients in which stroke
volume was measured as determined from CT/MRI scans, there was a significant positive
correlation between plasma CE-OOH levels on day 1 and stroke volume (r=0.57, p<0.002).
Conclusions
Plasma CE-OOH assay provides a direct evidence for involvement of
free radicals and lipid peroxidation in human stroke, and may be useful in assessing both
stroke prognosis as well as the outcome of therapeutic interventions.
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