The effect of a free radical scavenger and platelet-activating factor antagonist on FFA accumulation in post-ischemic canine brain |
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Authors: | Dandan Sun Douglas Kintner James H. Fitzpatrick Sherrie E. Emoto Pierre G. Braquet Nicolas G. Bazan David D. Gilboe |
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Affiliation: | (1) Dept. of Neurological Surgery, University of Wisconsin Medical School, 4630 Medical Sciences Center, 1300 University Avenue, 53706-1532 Madison, WI;(2) Dept. of Physiology, University of Wisconsin Medical School, 4630 Medical Sciences Center, 1300 University Avenue, 53706-1532 Madison, WI;(3) Dept. of Anesthesiology, University of Wisconsin, 53706 Madison, WI;(4) Biometry and Field Studies Branch NINDS/NIH, Bethesda, MD;(5) Institute Henri Beaufour, Paris, France;(6) LSU Eye Center, New Orleans, LA |
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Abstract: | The effects of the platelet-activating factor antagonist BN 50739 and a free radical scavenger dimethyl sulfoxide on the accumulation of free fatty acids in post-ischemic canine brain are reported. Following 14 min of complete normothermic ischemia and 60 min of reperfusion, the total brain FFAs were approximately 150% higher than in the control group (p<0.05). Perfusion with the platelet-activating factor antagonist BN50739 in its diluent dimethyl sulfoxide during 60 min of post-ischemic reoxygenation resulted in a 61.8% (p<0.01) reduction in the total brain free fatty acid accumulation. Palmitic, stearic, oleic, linoleic, and arachidonic acids decreased by 53.8%, 63.5%, 69.0%, 47.4%, and 57.2%, respectively. Although dimethyl sulfoxide alone caused stearic and arachidonic acids to return to the normal concentration range, BN 50739 had a significant influence on recovery of palmitic, oleic, and linoleic acids and was previously shown to provide significant therapeutic protection against damage to brain mitochondria following an ischemic episode. Because free fatty acid accumulation is one of the early phenomena in cerebral ischemia, this study provides evidence to support the hypothesis that both platelet-activating factor and free radicals are involved in initiating cerebral ischemic injury. |
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Keywords: | Free fatty acids ischemia BN 50739 pharmacoprotection |
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