oc-5186 and Ischemic-Attack--Transient

A new oligomeric derivative was synthesized from prostaglandin B2 and ascorbic acid, and its effect on rat brain ischemia-reperfusion injury was studied. Brain ischemia was produced in the rat by the combination of bilateral common carotid artery occlusion and hemorrhagic hypotension (30 mmHg, 20 min). The cerebral cortex was homogenized in the presence of the spin trap agent, N-tert-butyl-alpha-phenyl-nitrone (PBN). Spin-adducts were detected using an electron spin resonance spectrometer (EPR). Lipid peroxidation was estimated from the amounts of both thiobarbituric acid reactive substances (TBAR) and conjugated diene. In control experiments, reperfusion induced a burst of free radical formation which peaked at 5 min reperfusion time (238 +/- 41%). Lipid peroxidation increased significantly after 20 min of reperfusion (TBAR, 161 +/- 50%; conjugated diene, 160 +/- 29%). When the oligomeric derivative was administered (9 mg/kg i.p. 30 min before ischemic insult), it significantly reduced both spin adduct formation (103 +/- 13%) and lipid peroxidation (TBAR, 109 +/- 14%; conjugated diene, 97 +/- 33%).

Topics: Animals; Antioxidants; Blood Pressure; Cerebral Cortex; Electroencephalography; Electron Spin Resonance Spectroscopy; Free Radicals; Heart Rate; Ischemic Attack, Transient; Lipid Peroxidation; Male; Prostaglandins B; Rats; Rats, Inbred Strains; Reperfusion Injury

Two ester-type prostaglandin oligomeric compounds were synthesized, one from prostaglandin E1 (termed MR-356) and the other from prostaglandin B2 (termed OC-5186). Using in vivo [31P]MRS, the protective effects of these oligomers on forebrain ischemia (15 min) were evaluated in a rat model. Forebrain ischemia caused a decrease in intracellular high energy phosphates and intracellular pH (pHi) in the control and compounds-treated groups, but changes of these values in the OC-5186-treated group were significantly smaller than those in the control group. Moreover, the cerebral energy metabolism of the OC-5186-treated group returned to the preischemia level more rapidly than in the control group after forebrain ischemia. MR-356 had some effects, but the differences were not significant.

Topics: Adenosine Triphosphate; Alprostadil; Analysis of Variance; Animals; Brain; Energy Metabolism; Hydrogen-Ion Concentration; Ischemic Attack, Transient; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Phosphorus; Prostaglandins; Prostaglandins B; Rats; Rats, Inbred Strains; Time Factors