Effects of tirilazad mesylate on postischemic brain lipid peroxidation and recovery of extracellular calcium in gerbils

Edward D. Hall, Kay E. Pazara, J. Mark Braughler

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

We describe the effects of the 21-aminosteroid tirilazad mesylate (U-74006F) on postischemic lipid peroxidation (depletion of brain vitamin E) and cortical extracellular calcium recovery in gerbils subjected to 3 hours of unilateral carotid artery occlusion. Male gerbils were treated with either 0.2 ml vehicle (0.05N HC1) or 10 mg/kg i.p. U-74006F 10 minutes before the induction of ischemia and again immediately after the initiation of reperfusion. In the first series of experiments, the brain concentration of vitamin £, which was unaffected by ischemia without re perfusion, was decreased after 2 hours of reperfusion by an average of 60% in vehicle-treated animals compared with sham-operated animals; in the U-74006F—treated gerbils, the 2-hour postischemic vitamin £ loss was only 27% (p<0.002 different from vehicle-treated animals). In the second series, unilateral carotid artery occlusion produced a decrease in the cortical extracellular calcium concentration from 1.05 mM before ischemia to 0.11 mM by the end of the ischemic episode in both vehicle-and U-74006F-treated gerbils. After 2 hours of reperfusion, the calcium concentration had recovered to only 0.22 mM in the vehicle-treated animals compared with 0.56 mM in the U-74006F-treated group (p<0.01). Cortical blood flow, mean arterial blood pressure, and blood gases did not differ significantly between the two treatment groups. Administration of only the immediate postreperfusion dose (i.e., no pretreatment) also significantly improved the recovery of cortical extracellular calcium. The results indicate that U-74006F inhibits postischemic lipid peroxidation as assessed by the preservation of brain vitamin E and that, secondary to this membrane-protective effect, the processes responsible for the reversal of ischemia-triggered intracellular calcium accumulation are preserved.

Original languageEnglish
Pages (from-to)361-365
Number of pages5
JournalStroke
Volume22
Issue number3
DOIs
StatePublished - Mar 1991

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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