The Effect of Tirizad Mesylate on Brain Lipid Peroxidation Following Cerebral Ischemia in Gerbils
Hathaway, Darren P.
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Due to the vast clinical potential of the novel 21- aminosteroid analogs to reduce cerebral damage following an ischemIc event, a greater knowledge of their mechanism of action is desirable. This study was designed to elucidate the role of lipid peroxidation in the destruction of cerebral tissue and to determine if the cytoprotective action of the 21-aminosteroids was through inhibition of lipid peroxidation. Computer assisted image analysis was used to quantitate the extent of lipid peroxidation and tissue death following 3 hours of unilateral carotid occlusion (UCO) in the Mongolian gerbil. A dihydroxydiphenylamine chromogenic substrate was used in a novel histochemical procedure to stain lipid peroxides in coronal slices of ischemic brain. At 24 hours of reperfusion, lipid peroxides were present in 30% of the brain slice of vehicle treated animals. Peroxides were localized predominantly in the cerebral cortex of the ischemic hemisphere. Similarly, 2, 3, 5-triphenyl tetrazolium chloride (TTC) histochemistry showed that 35% of the coronal section was damaged by the ischemic event. Treatment with Tirilazad Mesylate (U- 74006F) immediately before and immediately after a 3 hour UCO had no statistically significant effect on the extent of lipid peroxidation in the ischemic hemisphere. These data suggest that the reported cytoprotective potential of U-74006F is mediated through mechanisms other than via direct chemical inhibition of lipid peroxidation.