Lazaroid U-74389G attenuates edema in rat brain subjected to post-ischemic reperfusion injury

Abstract

The aim of the present study was to determine the potential therapeutic value of 21-aminosteroid U-74389G, on blood–brain barrier (BBB) breakdown and edema in association with the changes in synaptosomal Na +/K + and Mg 2+/Ca 2+-ATPase activities in rat brain subjected to post-ischemic reperfusion injury. Brain ischemia was achieved by means of four-vessel occlusion model for 25 min and animals were sacrificed after 12 h reperfusion. An increase of cerebral tissue water content, blood–brain disruption and the changes of synaptosomal Na +/K + and Mg 2+/Ca 2+-ATPases activities were evaluated. U-74389G was given intraperitoneally at two times as 5 mg/kg at 10 min prior to ischemia and at the beginning of reperfusion. Edema was determined by means of wet-dried weight method, and BBB of extravasation of Evan's blue dye. Extravasation of Evan's blue dye into brain following ischemia and reperfusion was 2.4-fold of control value and brought close to control levels by the effect of U-74389G ( p<0.001). Post-ischemic reperfusion injury caused an increase of 3.7% in tissue water content of whole brain and administration of U-74389G lowered the cerebral edema ( p<0.001). The loses in the Na +/K +-ATPase and Mg 2+/Ca 2+-ATPase activities occurred as 42.1% ( p<0.01) and 65.7% ( p<0.001) of control value, respectively. While Mg 2+/Ca 2+-ATPase activity was enhanced compared to vehicle-treated group of animals ( p<0.01), Na +/K +-ATPase activity was fully recovered when compared to control by U-74389G ( p>0.05). U-74389G also significantly attenuated neuronal necrosis ( p<0.001) which was determined in the hippocampal CA1 subfield. Blood–brain barrier protection, attenuation of brain edema and neuronal necrosis concomitant with the stabilizing of membrane-bound enzymes brought about by the effect of U-74389G suggest that 21-aminosteroids are worthy of consideration in the acute treatment of cerebral ischemia.