SpringerLink
Log in

Increased high-mobility group box 1 levels are associated with depression after acute ischemic stroke

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Background and purpose

Increased high-mobility group box 1 (HMGB1) levels were found in patients after acute ischemic stroke. The aim of this study was to examine whether the circulating HMGB1 levels could predict the 3-month post-stroke depression (PSD).

Methods

The subjects were first-ever ischemic stroke patients who were hospitalized during the period from July 2020 to December 2020. HMGB1 concentrations were measured by enzyme-linked immunosorbent assay after admission. A 24-item Hamilton Depression Rating Scale was performed to evaluate PSD at 3 months after stroke.

Results

The analyses included 324 participants (mean age, 63.7 years; 171 male). Ninety-four patients (29.0%) were diagnosed as having PSD at 3 months. The median serum HMGB1 levels at admission was 7.5 ng/mL (IQR, 4.4–11.3 ng/mL). The PSD distribution across the HMGB1 quartiles ranged between 17.5% (first quartile) and 57.5% (fourth quartile). After covariate adjustments, the fourth quartile of HMGB1 was found to be associated with a higher risk of PSD (as compared with first HMGB1 quartile, odd ratio, 1.26; 95% confidence interval [CI], 1.17–1.35; P < 0.001). The area under the receiver operating characteristic curve of HMGB1 was 0.726 (95% CI 0.660–0.792) for PSD. Similar results were found when HMGB1 was analyzed as continuous variable. Furthermore, the optimal cutoff point of circulating HMGB1 levels was 8.6 ng/mL, with a sensitivity of 69.2% and a specificity of 73.9%.

Conclusions

This study demonstrated that higher HMGB1 levels in the acute phase of ischemic stroke were associated with increased risk of PSD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author.

References

  1. GBD 2016 (2019) Stroke Collaborators. Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 18(5):439–58

    Article  Google Scholar 

  2. Giroud M, Jacquin A, Béjot Y (2014) The worldwide landscape of stroke in the 21st century. Lancet 383:195–197

    Article  PubMed  Google Scholar 

  3. Zhang X, Tang Y, **e Y et al (2017) Total magnetic resonance imaging burden of cerebral small-vessel disease is associated with post-stroke depression in patients with acute lacunar stroke. Eur J Neurol 24:374–380

    Article  CAS  PubMed  Google Scholar 

  4. Hackett M, Pickles K (2014) Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies. Int J Stroke 9:1017–1025

    Article  PubMed  Google Scholar 

  5. Hackett M, Yapa C, Parag V, Anderson C (2005) Frequency of depression after stroke: a systematic review of observational studies. Stroke 36:1330–1340

    Article  PubMed  Google Scholar 

  6. Robinson R, Jorge R (2016) Post-stroke depression: a review. Am J Psychiatry 173:221–231

    Article  PubMed  Google Scholar 

  7. Cai W, Mueller C, Li Y, Shen W, Stewart R (2019) Post stroke depression and risk of stroke recurrence and mortality: a systematic review and meta-analysis. Ageing Res Rev 50:102–109

    Article  PubMed  Google Scholar 

  8. Villa R, Ferrari F, Moretti A (2018) Post-stroke depression: mechanisms and pharmacological treatment. Pharmacol Ther 184:131–144

    Article  CAS  PubMed  Google Scholar 

  9. Klune J, Dhupar R, Cardinal J, Billiar T, Tsung A (2008) HMGB1: endogenous danger signaling. Mol Med 14:476–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lu B, Wang C, Wang M et al (2014) Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review. Expert Rev Clin Immunol 10:713–727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fonken L, Frank M, Kitt M et al (2016) The Alarmin HMGB1 mediates age-induced neuroinflammatory priming. J Neurosci 36:7946–7956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Harris H, Andersson U, Pisetsky D (2012) HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol 8:195–202

    Article  CAS  PubMed  Google Scholar 

  13. Singh V, Roth S, Veltkamp R, Liesz A (2016) HMGB1 as a key mediator of immune mechanisms in ischemic stroke. Antioxid Redox Signal 24:635–651

    Article  CAS  PubMed  Google Scholar 

  14. Yang Q, Wang J, Li J et al (2010) High-mobility group protein box-1 and its relevance to cerebral ischemia. J Cereb Blood Flow Metab 30:243–254

    Article  PubMed  Google Scholar 

  15. Zhang J, Takahashi H, Liu K et al (2011) Anti-high mobility group box-1 monoclonal antibody protects the blood-brain barrier from ischemia-induced disruption in rats. Stroke 42:1420–1428

    Article  CAS  PubMed  Google Scholar 

  16. Schulze J, Zierath D, Tanzi P et al (2013) Severe stroke induces long-lasting alterations of high-mobility group box 1. Stroke 44:246–248

    Article  CAS  PubMed  Google Scholar 

  17. Lian Y, Gong H, Wu T et al (2017) Ds-HMGB1 and fr-HMGB induce depressive behavior through neuroinflammation in contrast to nonoxid-HMGB1. Brain Behav Immun 59:322–332

    Article  CAS  PubMed  Google Scholar 

  18. Lei C, Geng J, Zhong L (2020) The association between plasma HMGB1 and sRAGE and clinical outcome in intracerebral hemorrhage. J Neuroimmunol 15(345):577266

    Article  Google Scholar 

  19. Tsukagawa T, Katsumata R, Fujita M et al (2017) Elevated serum high-mobility group box-1 protein level is associated with poor functional outcome in ischemic stroke. J Stroke Cerebrovasc Dis 26:2404–2411

    Article  PubMed  Google Scholar 

  20. Brott T, Adams HJ, Olinger C et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20:864–870

    Article  CAS  PubMed  Google Scholar 

  21. Adams HJ, Bendixen B, Kappelle L, Biller J, Love B, Gordon D (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24(1):35–41

    Article  PubMed  Google Scholar 

  22. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang G, Zhou Y, Bu X et al (2019) Antiphospholipid antibodies predict post-stroke depression after acute ischemic stroke. J Affect Disord 257:160–165

    Article  PubMed  Google Scholar 

  24. Chen Y, Qu J, **ao W et al (2016) Intracranial atherosclerosis and poststroke depression in Chinese patients with ischemic stroke. J Stroke Cerebrovasc Dis 25:998–1004

    Article  PubMed  Google Scholar 

  25. Wang J, Jiang Y, Zeng D, Zhou W, Hong X (2020) Prognostic value of plasma HMGB1 in ischemic stroke patients with cerebral ischemia-reperfusion injury after intravenous thrombolysis. J Stroke Cerebrovasc Dis 29(9):105055

    Article  PubMed  Google Scholar 

  26. Wu T, Liu L, Zhang W et al (2015) High-mobility group box-1 was released actively and involved in LPS induced depressive-like behavior. J Psychiatr Res 64:99–106

    Article  PubMed  Google Scholar 

  27. Ye Y, Zeng Z, ** T, Gu L (2019) The role of high mobility group box 1 in ischemic stroke. Front Cell Neurosci 13:127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang C, Jiang J, Zhang X, Song L, Sun K, Xu R (2016) Inhibiting HMGB1 reduces cerebral ischemia reperfusion injury in diabetic mice. Inflammation 39:1862–1870

    Article  CAS  PubMed  Google Scholar 

  29. Bonanno G, Raiteri L, Milanese M et al (2007) The high-mobility group box 1 cytokine induces transporter-mediated release of glutamate from glial subcellular particles (gliosomes) prepared from in situ-matured astrocytes. Int Rev Neurobiol 82:73–93

    Article  CAS  PubMed  Google Scholar 

  30. Campos F, Sobrino T, Ramos-Cabrer P et al (2011) Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study. J Cereb Blood Flow Metab 31:1378–1386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cheng S, Zhao Y, Li J, Chen X, Wang R, Zeng J (2014) Plasma levels of glutamate during stroke is associated with development of post-stroke depression. Psychoneuroendocrinology 47:126–135

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Wanying Shan and Liang Xu equally contribute to this work

Authors and Affiliations

  1. Department of Neurology, Suzhou Ninth People’s Hospital, Soochow University, No. 2666 Ludang Road, Suzhou, 215200, Jiangsu, China

    Wanying Shan, Zhuoyin Qiu, **gwen Wang, Jiaxing Shao & Jie Feng

  2. Department of Anesthesiology, the First Affiliated Hospital of Soochow University, No.899 **hai Road, Suzhou, 215000, Jiangsu, China

    Liang Xu

  3. Department of Gerontology, Suzhou Ninth People’s Hospital, Soochow University, No. 2666 Ludang Road, Suzhou, 215200, Jiangsu, China

    Jie Zhao

Authors
  1. Wanying Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhuoyin Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. **gwen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiaxing Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jie Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jie Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jie Feng or Jie Zhao.

Ethics declarations

Ethics approval

The study was approved by the ethics committee of the Suzhou Ninth People’s Hospital.

Consent to participate

The patients gave written informed consent before entering the study.

Conflict of interest

None.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shan, W., Xu, L., Qiu, Z. et al. Increased high-mobility group box 1 levels are associated with depression after acute ischemic stroke. Neurol Sci 43, 3131–3137 (2022). https://doi.org/10.1007/s10072-021-05571-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-021-05571-x

Keywords

Search

Navigation