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Li Y.,Huazhong University of Science and Technology | Xu X.-L.,Huazhong University of Science and Technology | Xu X.-L.,The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province | Zhao D.,Huazhong University of Science and Technology | And 7 more authors.
CNS Neuroscience and Therapeutics

Aims: Brain ischemia activates astrocytes in a process known as astrogliosis. Although this process has beneficial effects, excessive astrogliosis can impair neuronal recovery. Polyinosinic-polycytidylic acid (Poly IC) has shown neuroprotection against cerebral ischemia-reperfusion injury, but whether it regulates reactive astrogliosis and glial scar formation is not clear. Methods: We exposed cultured astrocytes to oxygen-glucose deprivation/reoxygenation (OGD/R) and used a rat middle cerebral artery occlusion (MCAO)/reperfusion model to investigate the effects of Poly IC. Astrocyte proliferation and proliferation-related molecules were evaluated by immunostaining and Western blotting. Neurological deficit scores, infarct volumes and neuroplasticity were evaluated in rats after transient MCAO. Results: In vitro, Poly IC inhibited astrocyte proliferation, upregulated Toll-like receptor 3 (TLR3) expression, upregulated interferon-β, and downregulated interleukin-6 production. These changes were blocked by a neutralizing antibody against TLR3, suggesting that Poly IC function is TLR3-dependent. Moreover, in the MCAO model, Poly IC attenuated reactive astrogliosis, reduced brain infarction volume, and improved neurological function. In addition, Poly IC prevented MCAO-induced reductions in soma size, dendrite length, and number of dendritic bifurcations in cortical neurons of the infarct penumbra. Conclusions: By ameliorating astrogliosis-related damage, Poly IC is a potential therapeutic agent for attenuating neuronal damage and promoting recovery after brain ischemia. © 2015 John Wiley & Sons Ltd. Source

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