Fish oil provides robust and sustained memory recovery after cerebral ischemia: influence of treatment regimen.

We previously reported that long-term treatment with fish oil (FO) facilitates memory recovery after transient, global cerebral ischemia (TGCI), despite the presence of severe hippocampal damage. The present study tested whether this antiamnesic effect resulted from an action of FO on behavioral performance itself, or whether it resulted from an anti-ischemic action. Different treatment regimens were used that were distinguished from each other by their initiation or duration with regard to the onset of TGCI and memory assessment. Naive rats were trained in an eight-arm radial maze, subjected to TGCI (4-VO model, 15 min), and tested for memory performance up to 6 weeks after TGCI. Fish oil (docosahexaenoic acid, 300 mg/kg/day) was given orally according to one of the following regimens: regimen 1 (from 3 days prior to ischemia until 4 weeks post-ischemia), regimen 2 (from 3 days prior to ischemia until 1 week post-ischemia), and regimen 3 (from week 2 to week 5 post-ischemia). When administered according to regimens 1 and 2, FO abolished amnesia completely. This effect persisted for at least 5 weeks after discontinuing the treatment. Such an effect did not occur, however, in the group treated according to regimen 3. Hippocampal and cortical damage was not alleviated by FO. The present results demonstrate that FO-mediated memory recovery (or preservation) following TGCI is a reproducible, robust, and long-lasting effect. Moreover, such an effect was found with a relatively short period of treatment, provided it covered the first days prior to and after ischemia. This suggests that FO prevented amnesia by changing some acute, ischemia/reperfusion-triggered process and not by stimulating memory performance on its own.