Antioxidant CR-6 protects against reperfusion injury after a transient episode of focal brain ischemia in rats

Fernando J. Pérez-Asensio, Xavier De La Rosa, Francesc Jiménez-Altayó, Roser Gorina, Emili Martínez, Àngel Messeguer, Elisabet Vila, Àngel Chamorro, Anna M. Planas

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

Oxidative and nitrosative stress are targets for intervention after ischemia/reperfusion. The aim of this study was to explore the effect of CR-6, a vitamin-E analogue that is antioxidant and scavenger of nitrogen-reactive species. Sprague-Dawley rats had the middle cerebral artery (MCA) occluded either for 90 mins or permanently. Cortical perfusion was continuously monitored by laser-Doppler flowmetry. CR-6 (100 mg/kg) was administered orally either at 2 and 8 h after MCA occlusion, or at 2 h only. Infarct volume, neurological deficit, and signs of reperfusion injury were evaluated. CR-6 was detected in plasma and brain by HPLC. CR-6 reduced glutathione consumption in the ischemic brain and superoxide generation in the isolated MCA. CR-6 decreased infarct volume and attenuated the neurological deficit at 1 and 7 days after ischemia/reperfusion, but not after permanent ischemia. Immediately after reperfusion, cortical blood flow values returned to their baseline (±20%) in several animals, whereas others showed hyper-perfusion (>20% of baseline). Reactive hyperemia was associated with adverse events such as increased cortical BBB leakage, edema, protein nitrotyrosination, COX-2 expression, and neutrophil accumulation; and with a poorer outcome, and CR-6 attenuated these effects. In conclusion, oral CR-6 administration after transient ischemia protects the brain from reperfusion injury. © 2010 ISCBFM All rights reserved.
Original languageEnglish
Pages (from-to)638- 651
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number3
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Antioxidants
  • Hyperemia
  • Ischemia
  • Middle cerebral artery
  • Reperfusion
  • Stroke

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