[Effects of pentobarbital on brain lipid metabolism during global ischemia]

Abstract

It is known that pentobarbital, which has been used for severe brain infarct or head injury as a brain protective drug, inhibits the increase of free fatty acids (FFAs) liberated from membrane phospholipids during ischemia. However, the mechanisms of FFA liberation from phospholipids and the mode of action of pentobarbital are still unclear. Therefore we have investigated the effects of induction of global ischemia and pentobarbital pretreatment upon lipid metabolism in rat brain. Brain ischemia was evoked by rat decapitation and pentobarbital (60 mg/kg) was administered i.p. for 15 min prior to decapitation. Removed brains were incubated for 1, 5, 15 or 30 min at 37 degrees C and then quickly frozen in liquid nitrogen. After extraction of lipids from the brains, neutral lipid and phospholipid compositions were analyzed by thin-layer and gas-liquid chromatography. The results demonstrated that FFAs, either unsaturated or saturated, were rapidly accumulated in the brain during early period of ischemia, but attenuated significantly by pentobarbital pretreatment. Pentobarbital attenuated the accumulations of stearic and arachidonic acids, with little effect on palmitic and oleic acids. Diacylglycerol (DG), which is considered to be as a plausible candidate for the source of FFA, was also produced in the ischemic brain, and its acyl chain composition was similar to that of liberated FFAs. Furthermore, the increase of DG was inhibited significantly by pentobarbital anesthesia. In particular, pentobarbital attenuated the accumulation of DG enriched in arachidonic and stearic acids. This fatty acyl composition resembled the principal composition of phosphatidylinositol (PI) in rat brain.(ABSTRACT TRUNCATED AT 250 WORDS)