title: Detrimental effects of post-treatment with fatty acids on brain injury in ischemic rats.
abstract: Studies have illustrated that fatty acids, especially polyunsaturated fatty acids (PUFA), have a role in regulating oxidative stress via the enhancement of antioxidative defense capacity or the augmentation of oxidative burden. Elevated oxidative stress has been implicated in the pathogenesis of brain injury associated with cerebral ischemia/reperfusion (I/R). The objective of this study was to assess whether treatment with fatty acids after focal cerebral I/R induced by occlusion of the common carotid arteries and the middle cerebral artery has effects on brain injury in a rat model. PUFA, including arachidonic acid (AA) and docosahexaenoic acid (DHA), and the saturated fatty acid, stearic acid (SA), were administrated 60 min after reperfusion via intraperitoneal injection. AA and DHA aggravated cerebral ischemic injury, which manifested as enlargement of areas of cerebral infarction and increased impairment of motor activity, in a concentration-dependent manner. However, there were no remarkable differences in post-ischemic alterations between the SA and saline groups. The post-ischemic augmentation of injury in AA and DHA treatment groups was accompanied by increases in the permeability of the blood-brain barrier (BBB), brain edema, metalloproteinase (MMP) activity, inflammatory cell infiltration, cyclooxygenase 2 (COX-2) expression, caspase 3 activity, and malondialdehyde (MDA) production, and by a decrease in the brain glutathione (GSH) content. Furthermore, we found that either AA or DHA alone had little effect on free radical generation in neuroglia, but they greatly increased the hydrogen peroxide-induced oxidative burden. Taken together, these findings demonstrate the detrimental effect of PUFA such as AA and DHA in post-ischemic progression and brain injury after cerebral I/R is associated with augmentation of cerebral I/R-induced alterations, including oxidative changes.
authors.affiliation: Chang Bing Show Chwan Memorial Hospital, Changhua 542, Taiwan.
authors.forename: Dar-Yu
authors.initials: DY
authors.lastname: Yang
authors.forename: Hung-Chuan
authors.initials: HC
authors.lastname: Pan
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Yen
authors.forename: Chun-Chiang
authors.initials: CC
authors.lastname: Wang
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Chuang
authors.forename: Shih-Yun
authors.initials: SY
authors.lastname: Chen
authors.forename: Szu-Yin
authors.initials: SY
authors.lastname: Lin
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Liao
authors.forename: Shue-Ling
authors.initials: SL
authors.lastname: Raung
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Wu
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.forename: An-Na
authors.initials: AN
authors.lastname: Chiang
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D017536:Carotid Artery, Common / Q000601:surgery; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008026:Ligation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020768:Middle Cerebral Artery / Q000601:surgery; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013229:Stearic Acids / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D013229:Stearic Acids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C031183:stearic acid; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020782:Matrix Metalloproteinases; D005978:Glutathione