Association of circulating blood HMGB1 levels with ischemic stroke: a systematic review and meta-analysis

Neurol Res. 2018 Nov;40(11):907-916. doi: 10.1080/01616412.2018.1497254. Epub 2018 Jul 17.


Objectives: Inflammation plays a key role in the pathogenesis and progression of ischemic stroke (IS). The high mobility group box 1 (HMGB1) nucleoprotein is involved in the amplification of inflammatory responses during acute ischemic injury. HMGB1 levels in patients with active disease are higher than those in healthy controls. We performed a meta-analysis to assess currently published data pertaining to circulating blood HMGB1 levels in IS and the relationship with stroke severity.

Methods: We systematically searched for studies investigating the circulating blood HMGB1 levels in patients with IS in PubMed/Medline, Embase, the Cochrane Library, Web of science and China National Knowledge Infrastructure (CNKI). Two independent researchers used the Cochrane Collaboration tools for data extraction and quality assessment. Extracted data were analyzed by Review Manager version 5.3.

Results: A total of 28 studies were included with a total of 4497 participants, including 2671 IS patients and 1826 matched controls. The meta-analysis revealed that compared with control, IS patients had higher circulating blood HMGB1 levels (n = 4497, standardized mean difference (SMD) = 5.70, 95%confidence interval (CI) = 4.79 to 6.62, Z = 12.23, P < 0.00001), and the HMGB1 level was positively correlated with severity (n = 507, SMD = -2.12, 95%CI = -3.41 to -0.82, Z = 3.20, P < 0.00001) and infarct volume (n = 582, 95%CI = -4.06 to -1.70, Z = 4.79, P < 0.00001).

Conclusions: This meta-analysis demonstrates that circulating blood HMGB1 levels elevate in IS and higher HMGB1 levels may indicate a more serious condition.

Keywords: Ischemic stroke; circulating blood; high mobility group box 1; infarct volume; meta-analysis; severity.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Brain Ischemia / blood*
  • HMGB1 Protein / blood*
  • Humans
  • Stroke / blood*


  • Biomarkers
  • HMGB1 Protein
  • HMGB1 protein, human