Effect of long term administration of eicosapentaenoic acid (EPA) on survival, lipid metabolism, endothelium of middle cerebral artery (MCA) and experimental cerebral ischemia in stroke-prone spontaneously hypertensive rat (SHRSP)

Abstract

Effect of long term administration of eicosapentenoic acid (EPA) in stroke-prone spontaneously hypertensive rats (SHRSP) was studied. Survival, plasma lipid and endothelium of middle cerebral arteries (MCA) were investigated after administration of EPA for 25 weeks. Effect of EPA on acutely-induced cerebral ischemia was also studied. Eicosanoids play an important role in development of arteriosclerosis and occurrence of cerebral ischemia. EPA suppreses platelet aggregation and inhibits arachidonate conversion into thromboxane A₂and other prostaglandins. EPA is also itself oxidized by cyclooxygenase and lipoxygenase, and TXA₃ and LTB₅ derived from EPA show less potent biological actions compared to TXA₂ and LTB₄from arachidonate. Therefore administration of EPA might reduce development of arteriosclerosis and the brain damage from ischemic insult. The objective of this study is to investigate the effect of EPA on brain edema and metabolites in cerebral ischemia.
Eight weeks old male SHRSP were used for experiment. SHRSP were fed either a standard diet (control) or a diet supplemented with EPA (100 mg/kg/day) for 25 weeks. At 33 weeks old, plasma lipids were analyzed and luminal surfaces of MCA were investigated using scanning electron microscopy (SEM). In the same aged rats, cerebral ischemia was induced by bilateral common carotid artery occlusions (BLCO), and brain edema and metabolites (ATP, lactate, pyruvte) were determined 3 hr after BLCO.
In total plasma fatty acid composition, eicosapentaenoate (20:5) increased in the EPA administrated group, while the level of arachidonate (20:4) were not changed. In the SEM observation of MCA, a lot of microvilli, hypertrophy of marginal folds, shrinkage of endothelium and RBC trapped by fibrin nets were observed in the control group. While these degenerative changes were slight in the treated group. In the experiment of cerebral ischemia, brain water content in the EPA group was significantly lower and pyruvate was higher than in the control gorup, while there were no differences in the levels of ATP and lactate between the both groups.
These findings indicate that administration of EPA reduces ischemic damage, especially brain edema as well as degenerative changes of endothelium in non-ischemic SHRSP through influence on arachidonate metabolism.