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Progressive DNA and RNA damage from oxidation after aneurysmal subarachnoid haemorrhage in humans
Authors:Anders Jorgensen  Jonatan M Staalsoe  Anja H Simonsen  Steen G Hasselbalch  Peter Høgh  Allan Weimann
Institution:1. Psychiatric Centre Copenhagen, Copenhagen, Denmark;2. Department of Biomedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;3. Department of Neurology, University Hospital Bispebjerg, Copenhagen, Denmark;4. Danish Dementia Research Centre, Department of Neurology, University Hospital Rigshospitalet, Copenhagen, Denmark;5. Department of Biomedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;6. Danish Dementia Research Centre, Department of Neurology, University Hospital Rigshospitalet, Copenhagen, Denmark;7. Department of Neurology, University Hospital Zealand, Roskilde, Denmark;8. Laboratory of Clinical Pharmacology Q7642, University Hospital Rigshospitalet, Copenhagen, Denmark;9. Department of Clinical Pharmacology, University Hospital Bispebjerg, Copenhagen, Denmark
Abstract:Free radical toxicity is considered as a key mechanism in the neuronal damage occurring after aneurysmal subarachnoid haemorrhage (SAH). We measured markers of DNA and RNA damage from oxidation (8-oxodG and 8-oxoGuo, respectively) in cerebrospinal fluid from 45 patients with SAH on day 1–14 after ictus and 45 age-matched healthy control subjects. At baseline, both markers were significantly increased in patients compared to controls (p values?20-fold above control levels) from day 5–14. None of the markers predicted the occurrence of vasospasms or mortality, although there was a trend that the 8-oxoGuo marker was more strongly associated with mortality than the 8-oxodG marker. We conclude that SAH leads to a massive increase in damage to nucleic acids from oxidative stress, which is likely to play a role in neuronal dysfunction and death. As only patients in need of a ventriculostomy catheter were included in the study, the findings cannot necessarily be extrapolated to all patients with SAH.
Keywords:Aneurysm  nucleic acids  oxidative stress  subarachnoid haemorrhage  vasospasm
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