title: Immunomodulatory Effect of Toll-Like Receptor-3 Ligand Poly I:C on Cortical Spreading Depression.
abstract: 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.
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.|Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghaemi
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Sajadian
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Khodaie
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Ahmad Ali
authors.initials: AA
authors.lastname: Lotfinia
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Lotfinia
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Aghabarari
authors.affiliation: Klinik und Poliklinik für Neurochirurgie, WestfälischeWilhelms-Universität Münster, Münster, Germany.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khaleghi Ghadiri
authors.affiliation: Department of Neurology, WestfälischeWilhelms-Universität Münster, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Meuth
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran. gorjial@uni-muenster.de.|Institut für Physiologie I, WestfälischeWilhelms-Universität Münster, Münster, Germany. gorjial@uni-muenster.de.|Epilepsy Research Center, Universität Münster, Albert-Schweitzer-Campus 1, Gebäude: A1, 48149, Münster, Germany. gorjial@uni-muenster.de.
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology*; D017208:Rats, Wistar; D051196:Toll-Like Receptor 3 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011070:Poly I-C
keywords: Cell death; Immunotherapy; Migraine; Neuroprotection; Spreading depolarization; Stroke