Detrimental effects of post-treatment with fatty acids on brain injury in ischemic rats.
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.
Yang
Dar-Yu
DY
Chang Bing Show Chwan Memorial Hospital, Changhua 542, Taiwan.
Pan
Hung-Chuan
HC
Yen
Yu-Ju
YJ
Wang
Chun-Chiang
CC
Chuang
Yu-Han
YH
Chen
Shih-Yun
SY
Lin
Szu-Yin
SY
Liao
Su-Lan
SL
Raung
Shue-Ling
SL
Wu
Ching-Wen
CW
Chou
Ming-Chih
MC
Chiang
An-Na
AN
Chen
Chun-Jung
CJ
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
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