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Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression

Ghaemi, A. and Sajadian, A. and Khodaie, B. and Lotfinia, A.A. and Lotfinia, M. and Aghabarari, A. and Khaleghi Ghadiri, M. and Meuth, S. and Gorji, A. (2016) Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression. Molecular Neurobiology, 53 (1). pp. 143-154. ISSN 15591182

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The release of inflammatory mediators following cortical spreading depression (CSD) is suggested to play a role in pathophysiology of CSD-related neurological disorders. Toll-like receptors (TLR) are master regulators of innate immune function and involved in the activation of inflammatory responses in the brain. TLR3 agonist poly I:C exerts anti-inflammatory effect and prevents cell injury in the brain. The aim of the present study was to examine the effect of systemic administration of poly I:C on the release of cytokines (TNF-α, IFN-γ, IL-4, TGF-β1, and GM-CSF) in the brain and spleen, splenic lymphocyte proliferation, expression of GAD65, GABAAα, GABAAβ as well as Hsp70, and production of dark neurons after induction of repetitive CSD in juvenile rats. Poly I:C significantly attenuated CSD-induced production of TNF-α and IFN-γ in the brain as well as TNF-α and IL-4 in the spleen. Poly I:C did not affect enhancement of splenic lymphocyte proliferation after CSD. Administration of poly I:C increased expression of GABAAα, GABAAβ as well as Hsp70 and decreased expression of GAD65 in the entorhinal cortex compared to CSD-treated tissues. In addition, poly I:C significantly prevented production of CSD-induced dark neurons. The data indicate neuroprotective and anti-inflammatory effects of TLR3 activation on CSD-induced neuroinflammation. Targeting TLR3 may provide a novel strategy for developing new treatments for CSD-related neurological disorders. © 2014, Springer Science+Business Media New York.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: 4 aminobutyric acid A receptor; 4 aminobutyric acid B receptor; gamma interferon; glutamate decarboxylase 65; granulocyte macrophage colony stimulating factor; heat shock protein 70; interleukin 4; polyinosinic polycytidylic acid; toll like receptor 3; toll like receptor agonist; transforming growth factor beta1; tumor necrosis factor alpha, adult; animal experiment; animal model; animal tissue; antiinflammatory activity; Article; brain; brain ischemia; controlled study; cytokine production; cytokine release; entorhinal cortex; enzyme activation; innate immunity; lymphocyte proliferation; male; neuroprotection; nonhuman; protein expression; rat; spleen; spreading cortical depression; young adult
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 08 Sep 2016 05:53
Last Modified: 08 May 2018 06:46
URI: http://eprints.goums.ac.ir/id/eprint/4637

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