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.

Neurohistological and behavioral changes following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats.

Chronic cerebral hypoperfusion (CCH) may be a prodromal feature of aging-related dementias, and chronic hypertension is a major risk factor. We used a permanent, four-vessel occlusion/internal carotid artery (4-VO/ICA) model to evaluate the cognitive and neurohistological outcomes of CCH in both young and middle-aged rats. Young rats are asymptomatic after permanent 4-VO/ICA, and we tested the hypothesis that chronic hypertension aggravates the outcomes of CCH. Young normotensive rats (NTRs) and young spontaneously hypertensive rats (SHRs) were first subjected to 4-VO/ICA and then examined for hippocampal and cortical neurodegeneration 7, 15, and 30 days later. In a second experiment, both NTRs and SHRs were then trained in a modified, non-food-rewarded aversive radial maze (AvRM) task until acquiring asymptotic performance and then subjected to 4-VO/ICA. Thirty days later, they were assessed for memory retention of the previously acquired cognition. In a third, post hoc experiment, middle-aged NTRs were trained in the AvRM, subjected to 4-VO/ICA, and tested for memory retention 30 days later. Compared with NTRs, both SHRs and middle-aged NRTs had severe hippocampal and cortical damage, but they did not differ from each other, regardless of the chronicity of 4-VO/ICA. In contrast, NTRs were behaviorally asymptomatic, and retrograde memory performance was persistently impaired in SHRs. This amnesic effect in the SHR group was very similar to the middle-aged NTR group. These findings suggest that chronic hypertension deteriorates the capacity of the brain to adaptively respond to CCH. This influence of hypertension may parallel the effect of aging.