TLR3 ligand Poly IC Attenuates Reactive Astrogliosis and Improves Recovery of Rats after Focal Cerebral Ischemia

Yang Li, Xu Lin Xu, Dan Zhao, Lin Na Pan, Chun Wei Huang, Lian Jun Guo, Qing Lu, Jian Wang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalCNS Neuroscience and Therapeutics
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

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Keywords

  • Astrogliosis
  • Cerebral ischemia-reperfusion
  • Poly IC
  • TLR3
  • TLR4

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Physiology (medical)
  • Psychiatry and Mental health
  • Pharmacology

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