Research reportFish oil provides a sustained antiamnesic effect after acute, transient forebrain ischemia but not after chronic cerebral hypoperfusion in middle-aged rats

•Transient or chronic brain ischemia causes retrograde amnesia in middle-aged rats.•Fish oil (FO) given for 9 days after transient ischemia reversed retrograde amnesia.•The antiamnesic effect of FO persisted for 5 weeks after discontinuing treatment.•FO failed to prevent retrograde amnesia caused by chronic cerebral hypoperfusion.•FO serves to treat memory deficit after transient, but not chronic cerebral ischemia.

We reported that fish oil (FO) abolishes retrograde amnesia consistently following transient global cerebral ischemia (TGCI) in young rats, provided it covered the first days prior to and after ischemia. Here, we further evaluated whether FO given post-ischemia in older rats (15-18 months old) is equally effective in facilitating memory recovery. We also tested whether the antiamnesic effect of FO observed after TGCI can be reproduced after chronic cerebral hypoperfusion (CCH). FO (300 mg/kg docosahexaenoic acid [DHA]) was delivered orally 4 h after TGCI and continued once per day for 9 days. In the CCH group, FO treatment began soon after the first stage of 4-VO/ICA and continued daily for 43 days. Two weeks after surgery, the animals were tested for retrograde memory performance across 5 weeks. Both TGCI and CCH caused persistent memory impairment and hippocampal and cortical neurodegeneration. TGCI-induced retrograde amnesia was reversed by FO, an effect that was sustained for at least 5 weeks after discontinuing treatment. In contrast, the memory deficit caused by CCH remained unchanged after FO treatment. Both hippocampal and cortical damage was not alleviated by FO. We conclude that the FO-mediated antiamnesic effect following TGCI can be extended to older rats, even when the treatment begins 4 h postischemia. Such efficacy was not reproduced after CCH. Therefore, the present results support the notion that FO may have therapeutic utility in treating learning/memory dysfunction after acute/transient cerebral ischemia and suggest that such benefits may not apply when a state of chronic cerebrovascular insufficiency is present.