Biological Trace Element Research

, Volume 187, Issue 2, pp 482–491 | Cite as

Lanthanum Chloride Impairs the Blood-Brain Barrier Integrity by Reduction of Junctional Proteins and Upregulation of MMP-9 in Rats

  • Jie Wu
  • Jinghua Yang
  • Xiaobo Lu
  • Cuihong Jin
  • Shengwen Wu
  • Lijin Zhang
  • Xiaoyu Hu
  • Honglin Ma
  • Yuan CaiEmail author


Lanthanum could cause cognitive impairment in children and rodent animals. The normal blood-brain barrier (BBB) integrity is essential for protecting the brain from systemic toxins and maintaining the homeostasis for proper neuronal function. BBB dysfunction has been implicated as a potential mechanism of heavy metal-induced neurotoxicity. The present study was aimed to investigate effects of lanthanum on BBB integrity and endothelial junctional complexes in the cerebral cortex of young rats. Animals were exposed to lanthanum chloride (LaCl3) through drinking water under 0, 0.25, 0.5, and 1.0% concentrations from postnatal day 0 until 30 days after weaning. LaCl3-exposure increased BBB permeability, caused ultrastructure changes in cerebral capillaries, and reduced protein expression of claudin-5, occludin, and VE-cadherin. Due to the critical role of matrix metalloproteinases (MMPs) in BBB integrity, we further examined alterations in MMPs activity and expression. Enhanced gelatinase activity and upregulated MMP-9 expression were observed after LaCl3-exposure, concurrently with decreased expression of endogenous inhibitor tissue inhibitors of metalloproteinase (TIMP)-1. Taken together, this study demonstrated that postnatal lanthanum exposure caused leakage of BBB in young rats, partially attributed to upregulation of MMP-9 and reduction of junctional proteins expression.


Lanthanum Blood-brain barrier Tight junctions Matrix metalloproteinases 


Funding information

This work was supported by the National Natural Science Foundation of China; Grant Numbers are 81502837, 81673220, and 81273117.

Compliance with Ethical Standards

Ethical approval for all animals involved in this study was from the Institutional Animal Care and Use Committee of China Medical University.

Conflict of Interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jie Wu
    • 1
    • 2
  • Jinghua Yang
    • 1
  • Xiaobo Lu
    • 1
  • Cuihong Jin
    • 1
  • Shengwen Wu
    • 1
  • Lijin Zhang
    • 1
  • Xiaoyu Hu
    • 1
  • Honglin Ma
    • 2
  • Yuan Cai
    • 1
    Email author
  1. 1.Department of Toxicology, School of Public HealthChina Medical UniversityShenyangPeople’s Republic of China
  2. 2.Department of Occupational and Environmental Health, School of Public HealthJinzhou Medical UniversityJinzhouPeople’s Republic of China

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