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Antioxidant CR-6 protects against reperfusion injury after a transient episode of focal brain ischemia in rats.
- Source :
-
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2010 Mar; Vol. 30 (3), pp. 638-52. Date of Electronic Publication: 2009 Nov 11. - Publication Year :
- 2010
-
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.
- Subjects :
- Animals
Blood-Brain Barrier drug effects
Blood-Brain Barrier physiology
Blotting, Western
Brain Edema pathology
Brain Edema prevention & control
Brain Ischemia pathology
Cerebral Infarction pathology
Cerebrovascular Circulation physiology
Cyclooxygenase 2 metabolism
Hyperemia blood
Immunohistochemistry
Infarction, Middle Cerebral Artery pathology
Inflammation pathology
Leukocytes pathology
Male
Neutrophil Infiltration
Oxidative Stress drug effects
Psychomotor Performance physiology
RNA biosynthesis
RNA isolation & purification
Rats
Rats, Sprague-Dawley
Reactive Nitrogen Species metabolism
Reperfusion Injury pathology
Antioxidants pharmacology
Benzopyrans pharmacology
Brain Ischemia drug therapy
Neuroprotective Agents
Reperfusion Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1559-7016
- Volume :
- 30
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 19904289
- Full Text :
- https://doi.org/10.1038/jcbfm.2009.237