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

• Published in: Molecular neurobiology 2016-01, Vol.53 (1), p.143-154
• Main Authors: Ghaemi, Amir, Sajadian, Azadeh, Khodaie, Babak, Lotfinia, Ahmad Ali, Lotfinia, Mahmoud, Aghabarari, Afsaneh, Khaleghi Ghadiri, Maryam, Meuth, Sven, Gorji, Ali
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cerebral Cortex - metabolism; Cortical Spreading Depression - drug effects; Cortical Spreading Depression - immunology; Cytokines; Disease Models, Animal; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Immunotherapy; Ligands; Male; Migraine; Neurobiology; Neurology; Neurons - immunology; Neurosciences; Poly I-C - immunology; Poly I-C - pharmacology; Rats, Wistar; Stroke; Toll-Like Receptor 3 - immunology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-014-8995-z

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, GABA A α, GABA A β 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 GABA A α, GABA A β 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.