Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Abstract

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) 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 from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

• Authors: Y Matsuo, T Kihara, M Ikeda, M Ninomiya, H Onodera, K Kogure
• Journal: Brain research (Brain Res) Vol. 709 Issue 2 Pg. 296-302 (Feb 19 1996) ISSN: 0006-8993 [Print] Netherlands
• PMID: 8833766 (Publication Type: Journal Article)

Chemical References

• Azepines
• Bridged Bicyclo Compounds
• Fatty Acids, Monounsaturated
• Free Radicals
• Platelet Activating Factor
• Platelet Aggregation Inhibitors
• Reactive Oxygen Species
• Triazoles
• S 145
• 4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine
• Thromboxane A2
• semidehydroascorbic acid
• Peroxidase
• Ascorbic Acid
• Oxygen
• Dehydroascorbic Acid

Topics

• Animals
• Ascorbic Acid (metabolism)
• Azepines (pharmacology)
• Brain (metabolism)
• Brain Ischemia (metabolism)
• Bridged Bicyclo Compounds (pharmacology)
• Dehydroascorbic Acid (analogs & derivatives, antagonists & inhibitors, metabolism)
• Extracellular Space (metabolism)
• Fatty Acids, Monounsaturated (pharmacology)
• Free Radicals
• Male
• Oxygen (metabolism)
• Partial Pressure
• Peroxidase (metabolism)
• Platelet Activating Factor (antagonists & inhibitors, physiology)
• Platelet Aggregation Inhibitors (pharmacology)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Reperfusion
• Thromboxane A2 (antagonists & inhibitors, physiology)
• Triazoles (pharmacology)