title: Chloroquine pretreatment inhibits toll-like receptor 3 signaling after stroke.
abstract: Toll-like receptors (TLRs) mediated signaling is mainly implicated in inflammatory activation which contributes to the initiation and progression of stroke. Using a model of transient global cerebral ischemia (tGCI) in rats, we investigated the changes of pro-inflammation mediators and tested the effects of Chloroquine pretreatment on the expression of pro-inflammation mediators after stroke. Adult Male Sprague-Dawley (SD) rats were subjected to transient global cerebral ischemia (tGCI) and treated without or with Chiloquin pretreatment (60mg/kg) 2h before tGCI. Short-term spatial memory capacity, Western blot assay and semi-quantitive RT-PCR were performed. Compared to sham operated rats, tGCI rats showed worsened learning and memory capacity and increased expression of TLR3, interferon regulatory factor 3 (IRF3), and interferon β (IFN-β) in the Hippocampus after stroke. Chloroquine pretreatment significantly enhanced rats' short-term spatial memory capacity and attenuated the expression of TLR3, IFR3, and IFN-β in the Hippocampus compared to non-treatment control in tGCI rats. Therefore, Chloroquine pretreatment of stroke inhibits inflammatory response and improves short-term spatial memory capacity. The TLR3/IFR3-IFN-β signaling pathway may contribute to the reduced inflammatory response after stroke. Chloroquine warrants further investigation as a therapeutic agent for the treatment of stroke.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China. guiyuncui@foxmail.com
authors.forename: Guiyun
authors.initials: G
authors.lastname: Cui
authors.forename: Xinchun
authors.initials: X
authors.lastname: Ye
authors.forename: Tao
authors.initials: T
authors.lastname: Zuo
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Qiuchen
authors.initials: Q
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
mesh_terms: D000818:Animals; D002738:Chloroquine / Q000008:administration & dosage*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects*; D011292:Premedication / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D050838:Interferon Regulatory Factor-3; C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D002738:Chloroquine
keywords: Chloroquine; IFN-β; IFR3; Inflammatory response; Stroke; TLR3