Abstract--Prolonged ischemia by bilateral carotid artery ligation in rats resulted in cerebral edema with a reduced energy state. Mitochondria isolated from the ischemic brain showed an impairment of oxidative phosphorylation.The ischemic brain was also characterized by a remarkable accumulation of free fatty acids known to have properties as an uncoupling factor. The major components of increased free fatty acids were palmitic, stearic, oleic and arachidonic acids. The analysis of saponified myelin and mitochondrial lipids from the ischemic brain showed a decrease in fatty acid contents.The main components of decreased fatty acids in these subcellular fractions corresponded to those of free fatty acids accumulating in the ischemic brain. These results indicate that cerebral energy failure in the ischemic brain is related to the accumulation of free fatty acids, which are derived from endogenous brain lipids.Although considerable efforts have been devoted to the study on experimental brain edema, the biochemical alterations associated with the pathogenesis still remain to be eluci dated. Current evidence suggests that cerebral swelling is accompanied by a reduction of the cerebral energy state (1-3) and an impairment of mitochondrial function (4-6). A deficiency of available energy is assumed to cause a disturbance of active ionic transport across the cell membrane, which could lead to cerebral swelling or cell damage. In a previous report (7), we showed that unilateral brain edema produced in rats by the combination of ischemia and hypoxic exposure was characterized by a considerable increase of free fatty acids in the brain. Our experiments also demonstrated that oleic and arachidonic acids, which increased markedly in the edematous brain, inhibited oxidative phosphorylation of in vitro mitochondrial preparations (7). These observations provided information for further study on the biochemical mechanism of cerebral energy failure in brain edema.In the present study, we investigated cerebral energy metabolism in another form of brain edema produced in rats by a permanent ligation of bilateral carotid arteries. This paper deals with biochemical events associated with cerebral energy failure and the free fatty acid change in the subcellular lipids of the edematous brain.
MATERIALS AND METHODS
Brain ischennaMale Wistar rats weighing 80-100 g were anesthetized with sodium hexobarbital (150 mg/