The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province

Wuhan, China

The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province

Wuhan, China

Time filter

Source Type

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 | Year: 2015

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.

Loading The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province collaborators
Loading The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province collaborators