Molecular Neurobiology

, Volume 55, Issue 5, pp 4311–4319 | Cite as

Suppression of TLR4/NF-κB Signaling Pathway Improves Cerebral Ischemia–Reperfusion Injury in Rats

  • Hang Zhao
  • Zhuo Chen
  • Li-Juan Xie
  • Gui-Feng Liu


The present study aimed to investigate the effects of the toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-ҡB) signaling pathway in cerebral ischemia–reperfusion injury. A total of 125 male Sprague Dawley (SD) rats were selected for this study. Fifty SD rats were randomly divided into the control, sham injury, 0.5 h perfusion, 2 h perfusion, and 6 h perfusion groups to establish the model of ischemia–reperfusion. The rat brain injury model was established using the other 75 male SD rats, and different model groups with different treatments were established (15 rats per group): model control group (injected with 10 μL of saline solution), model + TAK-242 group (injected with resatorvid), model + PDTC group (injected with pyrrolidine dithiocarbamate), model + LPS group (injected with lipopolysaccharide), and sham injury group (incision to the neck skin and injected with 10 μL of saline solution for normal rats). These five groups were further assigned into three subgroups: day 3 group, day 7 group, and day 21 group. To determine how the TLR4/NF-қB signal pathway affects cerebral ischemia–reperfusion injuries, various methods including the Morris water maze, triphenyl tetrazolium chloride (TTC) staining, hematoxylin–eosin (HE) staining, and western blotting were employed in this study. No neurological deficit was observed in rats from the model control and sham injury groups. A slight neurological deficit was found in the 0.5 h reperfusion group, while in the 2 and 6 h perfusion groups, neurological dysfunction was evident. Compared to the sham injury group, the model control group displayed a longer escape latency (EL) and increased cerebral infarction volume and pathological changes with enhanced expression of TLR4 and NF-κB (all P < 0.05). The inhibition of the TLR4/NF-κB signal pathway shortened rat EL and diminished cerebral infarction volume, and the pathological changes became less evident (all P < 0.05), while the activation of the TLR4/NF-κB signal pathway elongated rat EL, enlarged infarction volume, and increased cerebral pathological change (all P < 0.05). Pearson correlation analysis demonstrated that TLR4/NF-κB expression is correlated with the extent of rat brain damage. Cerebral ischemia–reperfusion injury in rats can be alleviated via the inhibition of the TLR4/NF-κB signaling pathway.


Cerebral ischemia–reperfusion injury Lipopolysaccharide Neurological function NF-κB Pyrrolidine dithiocarbamate TLR4 



This study was supported by the National Youth Science Foundation (No. 80151459), the Science and Technology Development Plan of Jilin Provincial Science and Technology Department (No. 140520020JH), and the Thirteen Fifth Science and Technology Research Project in Jilin Education Department (No. 2016-467). We would like to acknowledge the helpful comments on this paper received from our reviewers.

Compliance With Ethical Standards

Animal experiments were conducted in strict accordance with the approved animal protocols and guidelines established by the Medical Ethics Review Committee for animal experiments [16]. All efforts were made to minimize the suffering of animals.

Competing Interests

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Hang Zhao
    • 1
  • Zhuo Chen
    • 1
  • Li-Juan Xie
    • 2
  • Gui-Feng Liu
    • 3
  1. 1.Department of NeurosurgeryChina-Japan Union Hospital of Jilin UniversityChangchunPeople’s Republic of China
  2. 2.Department of Vascular SurgeryChina-Japan Union Hospital of Jilin UniversityChangchunPeople’s Republic of China
  3. 3.Department of RadiologyChina-Japan Union Hospital of Jilin UniversityChangchunPeople’s Republic of China

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