S100ß, matrix metalloproteinase-9, D-dimer, and heat shock protein 70 are serologic biomarkers of acute cerebral infarction in a mouse model of transient MCA occlusion

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Abstract

Objective: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. Methods: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. Results: The average infarction volume was 12.32±2.31 mm3 and 46.9±7.43 mm3 in the 30-and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p<0.001) and neurological deficits (p<0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98). Conclusion: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

Original languageEnglish
Pages (from-to)548-558
Number of pages11
JournalJournal of Korean Neurosurgical Society
Volume61
Issue number5
DOIs
Publication statusPublished - 2018 Sep 1

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HSP70 Heat-Shock Proteins
Cerebral Infarction
Matrix Metalloproteinase 9
Biomarkers
Infarction
Area Under Curve
Serologic Tests
Brain Ischemia
ROC Curve
fibrin fragment D
Ischemia
Enzyme-Linked Immunosorbent Assay
Stroke
Sensitivity and Specificity

Keywords

  • Acute ischemic stroke
  • Biomarkers
  • Cerebral infarction volume

ASJC Scopus subject areas

  • Surgery
  • Neuroscience(all)
  • Clinical Neurology

Cite this

@article{987cb4794d2745179ef7e26e5185ddb9,
title = "S100{\ss}, matrix metalloproteinase-9, D-dimer, and heat shock protein 70 are serologic biomarkers of acute cerebral infarction in a mouse model of transient MCA occlusion",
abstract = "Objective: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. Methods: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. Results: The average infarction volume was 12.32±2.31 mm3 and 46.9±7.43 mm3 in the 30-and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p<0.001) and neurological deficits (p<0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98). Conclusion: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.",
keywords = "Acute ischemic stroke, Biomarkers, Cerebral infarction volume",
author = "Choi, {Jong Il} and Sung-Kon Ha and Lim, {Dong Jun} and Sang-Dae Kim and Se-Hoon Kim",
year = "2018",
month = "9",
day = "1",
doi = "10.3340/jkns.2017.0200",
language = "English",
volume = "61",
pages = "548--558",
journal = "Journal of Korean Neurosurgical Society",
issn = "2005-3711",
publisher = "Daehan sin'gyeong oe'gwa haghoe",
number = "5",

}

TY - JOUR

T1 - S100ß, matrix metalloproteinase-9, D-dimer, and heat shock protein 70 are serologic biomarkers of acute cerebral infarction in a mouse model of transient MCA occlusion

AU - Choi, Jong Il

AU - Ha, Sung-Kon

AU - Lim, Dong Jun

AU - Kim, Sang-Dae

AU - Kim, Se-Hoon

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Objective: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. Methods: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. Results: The average infarction volume was 12.32±2.31 mm3 and 46.9±7.43 mm3 in the 30-and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p<0.001) and neurological deficits (p<0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98). Conclusion: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

AB - Objective: Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. Methods: Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. Results: The average infarction volume was 12.32±2.31 mm3 and 46.9±7.43 mm3 in the 30-and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p<0.001) and neurological deficits (p<0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98). Conclusion: S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

KW - Acute ischemic stroke

KW - Biomarkers

KW - Cerebral infarction volume

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U2 - 10.3340/jkns.2017.0200

DO - 10.3340/jkns.2017.0200

M3 - Article

VL - 61

SP - 548

EP - 558

JO - Journal of Korean Neurosurgical Society

JF - Journal of Korean Neurosurgical Society

SN - 2005-3711

IS - 5

ER -