title: Eicosapentaenoic acid prevents memory impairment after ischemia by inhibiting inflammatory response and oxidative damage.
abstract: Previous studies have demonstrated that the generation of reactive oxygen species and an excessive inflammatory reaction are involved in the progression of neural damage following brain ischemia. In this study, we focused on the anti-inflammatory and antioxidant properties of eicosapentaenoic acid (EPA). Gerbils were treated intraperitoneally with 500 mg/kg of EPA ethyl for 4 weeks until the day of forebrain ischemia, which was induced by occluding the bilateral common carotid artery for 5 minutes. In the first part of the 2-part experiment, the effect of EPA treatment was evaluated using hematoxylin and eosin staining and deoxynucleotidyl transferase-mediated dUTP nick-end labeling as a marker of cell death (n=3 per group). The inflammatory reaction was evaluated using anti-Iba1 immunohistochemistry, a marker of microglial activation (n=3 per group), and detection of 8-hydroxyl-2'-deoxyguanosine, a marker of oxidative DNA damage (n=4 per group). In the second part of the experiment, the effect of EPA treatment on memory function was examined using an 8-arm radial maze (n=6 per group). EPA treatment significantly inhibited DNA oxidative damage (P < .05) and accumulation of Iba1-positive cells in the CA1 area at 12 and 72 hours after the induction of ischemia, and also decreased apoptotic neurons and neuronal death (P < .001) at 72 hours after ischemia. EPA treatment also significantly improved memory function (P < .05). These findings suggest that EPA inhibits the inflammatory reaction and oxidative damage occurring after ischemic brain injury, and also may contribute to the prevention of neural damage and memory impairment following such injury.
authors.affiliation: Department of Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Okabe
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Toyoshima
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyamoto
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Itano
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005849:Gerbillinae; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016548:Prosencephalon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015118:Eicosapentaenoic Acid; D003849:Deoxyguanosine