S100 beta, 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 S100 beta, 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 S100 beta, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. Results : The average infarction volume was 12.32 +/- 2.31 mm(3) and 46.9 +/- 7.43 mm (3) 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. S100 beta, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100 beta 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 S100 beta (AUC=0.98). Conclusion : S100 beta, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.