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 journalArticle

21 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 languageEnglish
Pages (from-to)4961-4971
JournalMolecular Neurobiology
Volume53
Issue number7
DOIs
Publication statusPublished - Sep 1 2016
Externally publishedYes

Keywords

  • Activated microglia
  • Cerebral ischemia
  • Etanercept
  • Stroke recovery
  • α-Lipoic acid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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