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Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3beta survival signaling.

Abstract
Recent studies have revealed that oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). However, how oxidative stress affects acute brain injury after SAH remains unknown. We have previously reported that overexpression of copper/zinc-superoxide dismutase (SOD1) reduces oxidative stress and subsequent neuronal injury after cerebral ischemia. In this study, we investigated the relationship between oxidative stress and acute brain injury after SAH using SOD1 transgenic (Tg) rats. SAH was produced by endovascular perforation in wild-type (Wt) and SOD1 Tg rats. Apoptotic cell death at 24 h, detected by a cell death assay, was significantly decreased in the cerebral cortex of the SOD1 Tg rats compared with the Wt rats. The mortality rate at 24 h was also significantly decreased in the SOD1 Tg rats. A hydroethidine study demonstrated that superoxide anion production after SAH was reduced in the cerebral cortex of the SOD1 Tg rats. Moreover, phosphorylation of Akt and glycogen synthase kinase-3beta (GSK3beta), which are survival signals in apoptotic cell death, was more enhanced in the cerebral cortex of the SOD1 Tg rats after SAH using Western blot analysis and immunohistochemistry. We conclude that reduction in oxidative stress by SOD1 overexpression may attenuate acute brain injury after SAH via activation of Akt/GSK3beta survival signaling.
AuthorsHidenori Endo, Chikako Nito, Hiroshi Kamada, Fengshan Yu, Pak H Chan
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 27 Issue 5 Pg. 975-82 (May 2007) ISSN: 0271-678X [Print] United States
PMID16969382 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Oxidants
  • Superoxides
  • Sod1 protein, rat
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
Topics
  • Animals
  • Animals, Genetically Modified
  • Apoptosis (drug effects)
  • Blood Gas Analysis
  • Blood Pressure (physiology)
  • Blotting, Western
  • Brain Diseases (etiology, pathology, prevention & control)
  • Fluorescent Antibody Technique
  • Glycogen Synthase Kinase 3 (physiology)
  • Glycogen Synthase Kinase 3 beta
  • Immunohistochemistry
  • Male
  • Oxidants (metabolism)
  • Oxidative Stress (physiology)
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt (physiology)
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction (physiology)
  • Subarachnoid Hemorrhage (complications, pathology, physiopathology)
  • Superoxide Dismutase (biosynthesis, genetics)
  • Superoxide Dismutase-1
  • Superoxides (metabolism)

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