TLR3 ligand Poly IC Attenuates Reactive Astrogliosis and Improves Recovery of Rats after Focal Cerebral Ischemia.
OBJECTIVE
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.
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yang
Y
Li
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China.
Xu-Lin
XL
Xu
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Dan
D
Zhao
Medical Department of Neurology, The Second Hospital of Nanchang, Nanchang, China.
Lin-Na
LN
Pan
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chun-Wei
CW
Huang
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China.
Lian-Jun
LJ
Guo
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China.
Qing
Q
Lu
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Jian
J
Wang
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D005911:Gliosis / Q000188:drug therapy*; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000188:drug therapy; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D007369:Interferon Inducers / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011070:Poly I-C / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D015427:Reperfusion Injury; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D007369:Interferon Inducers; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D005947:Glucose; D011070:Poly I-C
Astrogliosis; Cerebral ischemia-reperfusion; Poly IC; TLR3; TLR4