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Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation.

Abstract
A growing body of experimental data indicate that oxygen radicals may mediate the brain injury during ischemia-reperfusion. One potential source of oxygen radicals is activated neutrophils. To study the role of neutrophils in radical production during cerebral ischemia-reperfusion, we evaluated the effects of depletion of circulating neutrophils by administration of an anti-neutrophil monoclonal antibody (RP3) on radical formation in rats with 1-h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR decreased during MCA occlusion. After reperfusion, AR significantly increased at 30 min and 1 h, returned to near basal level until 2 h, and increased again at 24 h after reperfusion. In the rats treated with RP3, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, RP3 treatment completely inhibited the increase in extracellular AR after reperfusion. RP3 treatment exerted no effect on the changes in extracellular ascorbate or tissue PO2 throughout the experimental period. In conclusion, neutrophils are a major source of oxygen radicals during reperfusion after focal cerebral ischemia.
AuthorsY Matsuo, T Kihara, M Ikeda, M Ninomiya, H Onodera, K Kogure
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. 15 Issue 6 Pg. 941-7 (Nov 1995) ISSN: 0271-678X [Print] United States
PMID7593354 (Publication Type: Journal Article)
Chemical References
  • Free Radicals
  • Reactive Oxygen Species
  • semidehydroascorbic acid
  • Oxygen
  • Dehydroascorbic Acid
Topics
  • Animals
  • Brain (pathology, physiopathology)
  • Brain Ischemia (pathology, physiopathology)
  • Dehydroascorbic Acid (analogs & derivatives, metabolism)
  • Extracellular Space (metabolism)
  • Free Radicals (metabolism)
  • Leukocyte Count
  • Male
  • Neutrophils (cytology, physiology)
  • Oxygen (metabolism)
  • Partial Pressure
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species (metabolism)
  • Reperfusion

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