Chloroquine pretreatment inhibits toll-like receptor 3 signaling after stroke.

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.