Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke

Ming Hsiu Wu; Chao Ching Huang; Chung Ching Chio; Kuen Jer Tsai; Ching Ping Chang; Nan Kai Lin; Mao Tsun Lin

doi:10.1007/s12035-015-9418-5

Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke

Ming Hsiu Wu, Chao Ching Huang, Chung Ching Chio, Kuen Jer Tsai, Ching Ping Chang, Nan Kai Lin, Mao Tsun Lin

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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.

Original language	English
Pages (from-to)	4961-4971
Number of pages	11
Journal	Molecular Neurobiology
Volume	53
Issue number	7
DOIs	https://doi.org/10.1007/s12035-015-9418-5
Publication status	Published - Sept 1 2016

Keywords

Activated microglia
Cerebral ischemia
Etanercept
Stroke recovery
α-Lipoic acid

ASJC Scopus subject areas

Neurology
Cellular and Molecular Neuroscience

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10.1007/s12035-015-9418-5

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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.",

keywords = "Activated microglia, Cerebral ischemia, Etanercept, Stroke recovery, α-Lipoic acid",

author = "Wu, {Ming Hsiu} and Huang, {Chao Ching} and Chio, {Chung Ching} and Tsai, {Kuen Jer} and Chang, {Ching Ping} and Lin, {Nan Kai} and Lin, {Mao Tsun}",

note = "Funding Information: This study is supported in part by research grant Chi Mei Medical Center and NSC 101-2314-B-218-001-MY3 from the Taiwan National Science and Technology Department and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212-113002); China Medical University Hospital; Academia Sinica Taiwan Biobank; Stroke Biosignature Project (BM104010092); NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039-006-); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. Publisher Copyright: {\textcopyright} 2015, Springer Science+Business Media New York.",

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doi = "10.1007/s12035-015-9418-5",

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T1 - Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke

AU - Wu, Ming Hsiu

AU - Huang, Chao Ching

AU - Chio, Chung Ching

AU - Tsai, Kuen Jer

AU - Chang, Ching Ping

AU - Lin, Nan Kai

AU - Lin, Mao Tsun

N1 - Funding Information: This study is supported in part by research grant Chi Mei Medical Center and NSC 101-2314-B-218-001-MY3 from the Taiwan National Science and Technology Department and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212-113002); China Medical University Hospital; Academia Sinica Taiwan Biobank; Stroke Biosignature Project (BM104010092); NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039-006-); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. Publisher Copyright: © 2015, Springer Science+Business Media New York.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

KW - Activated microglia

KW - Cerebral ischemia

KW - Etanercept

KW - Stroke recovery

KW - α-Lipoic acid

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JO - Molecular Neurobiology

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Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke

Abstract

Keywords

ASJC Scopus subject areas

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