Effects of Toll-like receptor 4 inhibitor on hypoxic-ischemic hippocampal neurons and dendritic spines in neonatal rats

Xing ZHU; Zhen TANG; Xiying XIANG; Yanyan SUN; Bo WANG; Mingyan HEI

doi:10.16016/j.1000-5404.201910089

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Effects of Toll-like receptor 4 inhibitor on hypoxic-ischemic hippocampal neurons and dendritic spines in neonatal rats

更新时间：2026-01-09

- Effects of Toll-like receptor 4 inhibitor on hypoxic-ischemic hippocampal neurons and dendritic spines in neonatal rats
- Journal of Third Military Medical University Vol. 42, Issue 8, Pages: 815-821(2020)
- 作者机构：
- 作者简介：
- 基金信息：
  
  Supported by the General Program of National Natural Science Foundation of China(81671505);Natural Science Foundation of Beijing(7192061)
- DOI：10.16016/j.1000-5404.201910089
  CLC：
- Received：15 October 2019，
  
  Published：30 April 2020
- 稿件说明：
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Xing ZHU, Zhen TANG, Xiying XIANG, et al. Effects of Toll-like receptor 4 inhibitor on hypoxic-ischemic hippocampal neurons and dendritic spines in neonatal rats[J]. Journal of Third Military Medical University, 2020, 42(8): 815-821.
DOI：

Xing ZHU, Zhen TANG, Xiying XIANG, et al. Effects of Toll-like receptor 4 inhibitor on hypoxic-ischemic hippocampal neurons and dendritic spines in neonatal rats[J]. Journal of Third Military Medical University, 2020, 42(8): 815-821. DOI： 10.16016/j.1000-5404.201910089.

摘要

Abstract

Objective

To evaluate the effects of preconditioning with Toll-like receptor 4 (TLR4) inhibitor on hypoxic-ischemic hippocampal neurons and dendritic spines in neonatal rats.

Methods

Seventy-five neonatal (7-day-old) rats were randomly divided into control group

hypoxia-ischemia group (HI group) and TAK-242 (a TLR4-specific antagonist) group. In the latter 2 groups

rat models of hypoxic-ischemic brain damage (HIBD) were established using the Rice method

and in TAK-242 group

a single dose of TAK-242 (0.5 mg/kg) was intraperitoneally injected 30 min prior to HI. Western blotting was used to detect TLR4 expression in the left hippocampus of the rats 24 h after HI. On day 21 following the modeling

HE staining

Nissl staining and Golgi silver staining were used to assess neuronal loss and the changes in dendritic spine density in the left hippocampus. The expression of N-methyl-D-aspartic acid receptors 2A and 2B (NR2A and NR2B) was detected using Western blotting and immunofluorescence staining.

Results

The expression of TLR4 in the left hippocampus of the neonatal rats increased significantly at 24 h after HI (

0.05)

and TAK-242 obviously suppressed the up-regulated expression of TLR4 (

0.05). Compared with those in the control group

the number of neurons

dendritic spine density and the expression of NR2A all decreased significantly in the left hippocampus of the rats at 21 d after HI (

0.05); pretreatment with TAK-242 obviously alleviated these changes (

0.05).

Conclusion

TLR4 inhibitor can mitigate HI-induced long-term damage of the hippocampal neurons and the dendritic spines.

关键词

Keywords

references

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