title: Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke.
abstract: Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects of alpha-lipoic acid and etanercept given either singly or in combination in rats subjected to middle cerebral artery occlusion. Both α-lipoic acid and etanercept markedly reduced cerebral infarct, blood-brain barrier disruption, and neurological motor deficits with the former drug being more effective with the dosage used. Furthermore, when used in combination, the reduction was more substantial. Remarkably, a greater diminution in the serum levels of tumor necrosis factor-alpha as well as the brain levels of microglial activation (e.g., microgliosis, amoeboid microglia, and microglial overexpression of tumor necrosis factor-α) was observed with the combined drug treatment as compared to the drugs given separately. We conclude that inhibition of peripheral tumor necrosis factor-alpha as well as downregulation of brain microglial activation by alpha-lipoic acid or etanercept protect rat brain against ischemic stroke. Moreover, when both drugs were used in combination, the stroke recovery was promoted more extensively.
authors.affiliation: The Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.|Division of Neurology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, 736, Taiwan.
authors.forename: Ming-Hsiu
authors.initials: MH
authors.lastname: Wu
authors.affiliation: The Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.|Department of Pediatrics, National Cheng Kung University College of Medicine and Hospital, Tainan, 701, Taiwan.
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Chio
authors.affiliation: The Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Kuen-Jer
authors.initials: KJ
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan.
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Li-Sheng Biotechnology Co., Ltd., Taipei, Taiwan.
authors.forename: Nan-Kai
authors.initials: NK
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan. 891201@mail.chimei.org.tw.
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D000068800:Etanercept / Q000008:administration & dosage*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008063:Thioctic Acid / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D008063:Thioctic Acid; D000068800:Etanercept
keywords: Activated microglia; Cerebral ischemia; Etanercept; Stroke recovery; α-Lipoic acid