Recombinant human soluble thrombomodulin protects against brain injury in a CVST rat model, via downregulation of the HMGB1-RAGE axis

  • Authors:
    • Jian‑Jun Gu
    • Jie‑Bin Chen
    • Jian‑He Zhang
    • Hao Zhang
    • Shou‑Sen Wang
  • View Affiliations

  • Published online on: October 26, 2016     https://doi.org/10.3892/mmr.2016.5891
  • Pages: 5217-5222
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Cerebral venous sinus thrombosis (CVST) is a distinct cerebrovascular disorder, and ~50% of CVST patients progress to cerebral venous infarction, resulting in elevation of cerebral venous pressure. Anticoagulation is the standard initial treatment and is associated with a reduced relative risk of mortality and dependency. Recombinant human soluble thrombomodulin (rhs‑TM) is a promising therapeutic natural anticoagulant comparable to antithrombin, tissue factor pathway inhibitor, and activated protein C. The present study aimed to investigate the protective effects of rhs‑TM in a CVST rat model, and identify any underlying mechanisms. Rats were treated with rhs‑TM intravenously prior to CVST. Following neurological function evaluation, animals were sacrificed and brain water content and infarct volume were assessed. Brain tissue was collected from the infarcted segments and mRNA and protein expression levels of high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6, caspase‑3, B‑cell lymphoma‑2 and Bcl‑2 associated X were analyzed by reverse transcription-quantitative polymerase chain reaction and western blot analysis. rhs‑TM significantly prevented neurological deficits in locomotor function and reduced infarct volume. The expression levels of HMGB1‑RAGE were upregulated in the infarcted segments of rat brains following CVST. Pretreatment with rhs‑TM inhibited the HMGB1‑RAGE axis, alleviating the expression levels of the proinflammatory cytokines, TNF‑α, IL‑1β and IL‑6; however, expression levels of the apoptosis-associated genes and proteins remained unaffected. The results of the present study indicated that rhs‑TM protects against CVST in the rat model via inhibition of the HMGB1‑RAGE axis and inflammation, but not via apoptosis.
View Figures
View References

Related Articles

Journal Cover

December-2016
Volume 14 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Gu JJ, Chen JB, Zhang JH, Zhang H and Wang SS: Recombinant human soluble thrombomodulin protects against brain injury in a CVST rat model, via downregulation of the HMGB1-RAGE axis. Mol Med Rep 14: 5217-5222, 2016
APA
Gu, J., Chen, J., Zhang, J., Zhang, H., & Wang, S. (2016). Recombinant human soluble thrombomodulin protects against brain injury in a CVST rat model, via downregulation of the HMGB1-RAGE axis. Molecular Medicine Reports, 14, 5217-5222. https://doi.org/10.3892/mmr.2016.5891
MLA
Gu, J., Chen, J., Zhang, J., Zhang, H., Wang, S."Recombinant human soluble thrombomodulin protects against brain injury in a CVST rat model, via downregulation of the HMGB1-RAGE axis". Molecular Medicine Reports 14.6 (2016): 5217-5222.
Chicago
Gu, J., Chen, J., Zhang, J., Zhang, H., Wang, S."Recombinant human soluble thrombomodulin protects against brain injury in a CVST rat model, via downregulation of the HMGB1-RAGE axis". Molecular Medicine Reports 14, no. 6 (2016): 5217-5222. https://doi.org/10.3892/mmr.2016.5891