Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia/reperfusion injury by inhibiting ICAM-1 mRNA expression in rats

• Published in: Brain research 2008-05, Vol.1209, p.136-150
• Main Authors: Cheng, Chin-Yi, Su, Shan-Yu, Tang, Nou-Ying, Ho, Tin-Yun, Chiang, Su-Yin, Hsieh, Ching-Liang
• Format: Article
• Language: English
• Subjects: 4-Hydroxy-2-nonenal; 8-Hydroxy-2′-deoxyguanosine; Aldehydes - metabolism; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Brain Ischemia - physiopathology; Caspase 3 - metabolism; Coumaric Acids - pharmacology; Coumaric Acids - therapeutic use; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Disease Models, Animal; Encephalitis - drug therapy; Encephalitis - metabolism; Encephalitis - physiopathology; Ferulic acid; Free Radical Scavengers - pharmacology; Free Radical Scavengers - therapeutic use; Gene Expression - drug effects; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - physiopathology; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - genetics; Intercellular adhesion molecule-1 mRNA; Macrophage-1 Antigen - genetics; Macrophage-1 antigen mRNA; Male; Medical sciences; Nerve Tissue Proteins - metabolism; Neurology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Nuclear Proteins - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.02.090

Abstract Our previous studies have shown that ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) inhibits intercellular adhesion molecule-1 (ICAM-1) expression in the ischemic striatum after 2 h of reperfusion in a transient middle cerebral artery occlusion model in rats. The purpose of this study is to further investigate the neuroprotective effects of FA during reperfusion after cerebral ischemia. Rats were subjected to 90 min of ischemia; they were then sacrificed after 2, 10, 24 and 36 h of reperfusion. ICAM-1 and macrophage-1 antigen (Mac-1) mRNA were detected using semi-quantitative RT-PCR at 2 h of reperfusion. Mac-1, 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2′-deoxyguanosine (8-OHdG), active caspase 3, neuronal nuclei (NeuN) and TUNEL positive cells were measured at 2, 10, 24 and 36 h of reperfusion. FA (100 mg/kg, i.v.) administered immediately after MCAo inhibited ICAM-1 and Mac-1 mRNA expression in the striatum at 2 h of reperfusion, and reduced the number of Mac-1, 4-HNE and 8-OHdG positive cells in the ischemic rim and core at 10, 24 and 36 h of reperfusion. FA decreased TUNEL positive cells in the penumbra at 10 h, and in the ischemic boundary and core at 24 and 36 h of reperfusion. FA curtailed active caspase 3 expression in the penumbra at 10 h and restored NeuN-labeled neurons in the penumbra and ischemic core at 36 h of reperfusion. FA decreased the level of ICAM-1 mRNA and the number of microglia/macrophages, and subsequently down-regulated inflammation-induced oxidative stress and oxidative stress-related apoptosis, suggesting that FA provides neuroprotection against oxidative stress-related apoptosis by inhibiting ICAM-1 mRNA expression after cerebral ischemia/reperfusion injury in rats.