Analysis of F4-neuroprostanes, F2-isoprostanes, or Lipid-soluble Antioxidants in Humans and Rats following Non-traumatic Subarachnoid Hemorrhage

• Main Authors: Yu Ping Hsieh, 謝育萍
• Other Authors: H. C. Yen
• Format: Others
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/38297932565583355704

碩士 === 長庚大學 === 醫學生物技術研究所 === 96 === Aneurysmal subarachnoid hemorrhage (aSAH) caused by aneurysmal rupture is a major type of non-traumatic hemorrhagic stroke in humans. Following aSAH, patients may develope delayed ischemic neurological deficit leading to poor outcome. We hypothesized that oxidative stress would be increased following aSAH due to hemoglobin release and ischemic-reperfusion injury. F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NPs) are the most specific markers of lipid peroxidation derived from arachidonic acid and docosahexaenoic acid, respectively. Our previously published results showed that levels of F2-IsoPs in cerebrospinal fluid (CSF) of aSAH patients were higher than controls and positively correlated with poor clinical conditions or outcome. In the present study, we have established the first and only complete platform to analyze F2-IsoPs and F4-NPs by gas chromatography/negative-ion-chemical-ionization mass spectrometry in Taiwan. We then further investigated the role of neuronal oxidative damage in aSAH by detecting F4-NPs in CSF from 12 controls and 15 aSAH patients. CSF of patients were collected everyday after surgery for up to 10 days. The results showed that the levels of F4-NPs in aSAH patients were significantly higher than controls and positively correlated with severity of hemorrhage and poor outcome. Moreover, CSF F4-NPs levels in aSAH patients with death outcome had greater variations and unusual high values, especially at early time points, compared with F2-IsoPs. On the other hand, we also examined whether oxidative stress was increased in rats with vasospasm induced by experimental SAH. The oxidative stress was not different between sham-control and single-hemorrhage rats. However, coenzyme Q10 levels in plasma of double-hemorrhage models were significantly different from sham-control rats. In summary, our results provide the first evidence for oxidative damage to neurons and indicate that CSF F4-NPs could be a better marker than F2-IsoPs for predicting outcome in aSAH patients. The double-hemorrhage model to induce SAH in rats may be more appropriate to investigate the relationship between vasospasm and oxidative damage.