title: Fish oil provides a sustained antiamnesic effect after acute, transient forebrain ischemia but not after chronic cerebral hypoperfusion in middle-aged rats.
abstract: 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 4h 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 4h 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.
authors.affiliation: Department of Pharmacology and Therapeutic, Health Science Center, State University of Maringá, Maringá 87020-900, PR, Brazil.
authors.forename: Emilene Dias Fiuza
authors.initials: ED
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology and Therapeutic, Health Science Center, State University of Maringá, Maringá 87020-900, PR, Brazil.
authors.forename: Cássia Valério
authors.initials: CV
authors.lastname: Romanini
authors.affiliation: Department of Pharmacology and Therapeutic, Health Science Center, State University of Maringá, Maringá 87020-900, PR, Brazil.
authors.forename: Janaina Nicolau
authors.initials: JN
authors.lastname: de Oliveira
authors.affiliation: Department of Statistic, Exact Science Center, State University of Maringá, Maringá 87020-900, PR, Brazil.
authors.forename: Isolde Terezinha Santos
authors.initials: IT
authors.lastname: Previdelli
authors.affiliation: Department of Morphophysiological Sciences, Biological Science Center, State University of Maringá, Maringá 87020-900, PR, Brazil.
authors.forename: Silvana Regina
authors.initials: SR
authors.lastname: de Melo
authors.affiliation: Department of Pharmacology and Therapeutic, Health Science Center, State University of Maringá, Maringá 87020-900, PR, Brazil.
authors.forename: Rúbia Maria Weffort
authors.initials: RM
authors.lastname: de Oliveira
authors.affiliation: Department of Pharmacology and Therapeutic, Health Science Center, State University of Maringá, Maringá 87020-900, PR, Brazil. Electronic address: hmilani@uem.br.
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
mesh_terms: D000648:Amnesia, Retrograde / Q000188:drug therapy* / Q000209:etiology; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005395:Fish Oils / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000401:mortality; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
chemical_list: D005395:Fish Oils; D018696:Neuroprotective Agents
keywords: Antiamnesic effect; Chronic cerebral hypoperfusion; Fish oil; Functional recovery; Retrograde amnesia; Transient, Global cerebral ischemia