Research reportPostischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy

•Transient global cerebral ischemia (TGCI) induces retrograde amnesia and neuronal damage.•Fish oil (FO) prevented that amnesia with a time window of efficacy of up to 8 h.•FO failed to prevent ischemic cell death, but restored dendritic density in the hippocampus.•Dendritic plasticity in the CA3 subfield may contribute to the antiamnesic effect of FO after TGCI.

We reported that fish oil (FO) prevented the loss of spatial memory caused by transient, global cerebral ischemia (TGCI), provided the treatment covered the first days prior to and after ischemia. Continuing these studies, trained rats were subjected to TGCI, and FO was administered for 10 days, with a time window of efficacy (TWE) of 4, 8 or 12 h post-ischemia. Retrograde memory was assessed up to 43 days after TGCI. In another experiment, ischemic rats received FO with a 4- or 12-h TWE, and dendritic density was assessed in the hippocampus and cerebral cortex. The brain lipid profile was evaluated in sham-operated and ischemic rats that were treated with FO or vehicle with a 4-h TWE. Ischemia-induced retrograde amnesia was prevented by FO administration that was initiated with either a 4- or 8-h TWE. Fish oil was ineffective after a 12-h TWE. Independent of the TWE, FO did not prevent ischemic neuronal death. In the hippocampus, but not cerebral cortex, TGCI-induced dendritic loss was prevented by FO with a 4-h TWE but not 12-h TWE. The level of docosahexaenoic acid almost doubled in the hippocampus in ischemic, FO-treated rats (4-h TWE). The data indicate that (i) the anti-amnesic effect of FO can be observed with a TWE of up to 8 h, (ii) the stimulation of dendritic neuroplasticity may have contributed to this effect, and (iii) DHA in FO may be the main active constituent in FO that mediates the cognitive and neuroplasticity effects on TGCI.

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