Introduction:
Iron-dependent formation of reactive oxygen species has been implicated in the development of vasospasm (VSP) and neuronal injury following experimental subarachnoid hemorrhage (SAH). We report the association between unbound (“free”) iron in CSF of SAH patients and the risk of angiographic vasospasm and cerebral infarcts (CI) on neuroimaging from a recently completed pilot study.
Methods:
Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure redox active iron (REDOX-Fe). Ceruloplasmin (Cp) concentration and levels of malondialdehyde (MDA), a marker of lipid peroxidation were also measured. We prospectively collected and recorded demographic, clinical, and radiological data. Logistic regression and Wilcoxon Rank Sum test were used.
Results:
Five of 12 patients developed angiographic VSP (41.6%) and eight developed CI (66.6%). Mean REDOX-Fe was higher in patients with CI (3.96 ± 0.97 Vs. 2.77 ± 0.87 mcg/dl,
p
0.07), particularly in patients with deep-seated strokes (4.56 ± 0.67 Vs. 3.35 ± 0.89,
p
0.03). Levels of Cp at day 3 were lower in patients with deep strokes (34,092 ± 23,780 Vs. 86,045 ± 34,752 ng/ml,
p
0.03). A trend towards higher REDOX-Fe on day 3 in patients who developed VSP (4.52 ± 1.16 Vs. 2.96 ± 0.71,
p
0.07), and lower Cp levels on day 5 (45,033 ± 29,079 Vs. 63,044 ± 24,821,
p
0.1) was found. Levels of MDA were higher in patients who developed CI (10.36 ± 4.36 Vs. 5.9 ± 4.2 nmol,
p
0.08).
Conclusions:
In this preliminary study we found higher concentrations of redox active iron in CSF of SAH patients who develop deep-seated CI on neuroimaging. Evidence of increased oxidative damage correlated with development of CI. A possible association between non-protein bound iron and angiographic VSP is suggested as well. Ceruloplasmin may exert a protective effect in this setting. Further studies are needed to validate these findings.
Iron Redox Transformation by the Thermo-Acidophilic Archaea from the Genus Sulfolobus