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High-Mobility Group Box 1 Neutralization Prevents Chronic Cerebral Hypoperfusion-Induced Optic Tract Injuries in the White Matter Associated with Down-regulation of Inflammatory Responses

  • Yue Hei
  • Xin Zhang
  • Rong Chen
  • Yuefei Zhou
  • Dakuan Gao
  • Weiping LiuEmail author
Original Research

Abstract

Chronic cerebral hypoperfusion (CCH)-induced white matter lesions (WMLs) are region-specific with the optic tract (OT) displaying the most severe damages and leading to visual-based behavioral impairment. Previously we have demonstrated that anti-high-mobility group box 1 (HMGB1) neutralizing antibody (Ab) prevents CCH-induced hippocampal damages via inhibition of neuroinflammation. Here we tested the protective role of the Ab on CCH-induced OT injuries. Rats were treated with permanent occlusion of common carotid arteries (2-VO) or a sham surgery, and then administered with PBS, anti-HMGB1 Ab, or paired control Ab. Pupillary light reflex examination, visual water maze, and tapered beam-walking were performed 28 days post-surgery to investigate the behavioral deficits. Meanwhile, WMLs were measured by Klüver-Barrera (KB) and H&E staining, and glial activation was further assessed to evaluate inflammatory responses in OT. Results revealed that anti-HMGB1 Ab ameliorated the morphological damages (grade scores, vacuoles, and thickness) in OT area and preserved visual abilities. Additionally, the increased levels of inflammatory responses and expressions of TLR4 and NF-κB p65 and phosphorylated NF-κB p65 (p-p65) in OT area were partly down-regulated after anti-HMGB1 treatment. Taken together, these findings suggested that HMGB1 neutralization could ease OT injuries and visual-guided behavioral deficits via suppressing inflammatory responses.

Keywords

HMGB1 neutralization Chronic cerebral hypoperfusion Optic tract Glial activation NF-κB 

Notes

Acknowledgements

Informed consent was obtained from all individual participants included in the study. Besides, we wish to thank Xiaoyan Chen for technical support.

Author Contributions

YH and XZ performed the experiments, RC and YZ wrote the manuscript, DG and WL designed the experiments, and WL is responsible for the final version. All authors read and approved the final manuscript.

Funding

This research was supported by Natural Science Foundation of China (No. 81627806).

Compliance with Ethical Standards

Conflict of interest

No conflict of interest was declared.

Ethical Approval

National Institutes of Health Ethic Committee gave permission to the animal experiments, which were conducted in accordance with the National Experimental Animals Guidelines.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yue Hei
    • 1
  • Xin Zhang
    • 1
  • Rong Chen
    • 2
  • Yuefei Zhou
    • 1
  • Dakuan Gao
    • 1
  • Weiping Liu
    • 1
    Email author
  1. 1.Department of Neurosurgery, Xijing HospitalFourth Military Medical UniversityXi’anPeople’s Republic of China
  2. 2.Department of Neurology, Xijing HospitalFourth Military Medical UniversityXi’anPeople’s Republic of China

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