Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke

Svetlana A. Dambinova, Kerstin Bettermann, Theodore Glynn, Matthew Tews, David Olson, Joseph D. Weissman, Richard L. Sowell

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: The acute assessment of patients with suspected ischemic stroke remains challenging. The use of brain biomarker assays may improve the early diagnosis of ischemic stroke. The main goal of the study was to evaluate whether the NR2 peptide, a product of the proteolytic degradation of N-methyl-D-aspartate (NMDA) receptors, can differentiate acute ischemic stroke (IS) from stroke mimics and persons with vascular risk factors/healthy controls. A possible correlation between biomarker values and lesion sizes was investigated as the secondary objective. Methods and Findings: A total of 192 patients with suspected stroke who presented within 72 h of symptom onset were prospectively enrolled. The final diagnosis was determined based on clinical observations and radiological findings. Additionally gender- and age-matched healthy controls (n = 52) and persons with controlled vascular risk factors (n = 48) were recruited to compare NR2 peptide levels. Blinded plasma was assayed by rapid magnetic particles (MP) ELISA for NR2 peptide within 30 min and results for different groups compared using univariate and multivariate statistical analyses. There was a clinical diagnosis of IS in 101 of 192 (53%) and non-stroke in 91 (47%) subjects. The non-stroke group included presented with acute stroke symptoms who had no stroke (n = 71) and stroke mimics (n = 20). The highest NR2 peptide elevations where found in patients with IS that peaked at 12 h following symptom onset. When the biomarker cut off was set at 1.0 ug/L, this resulted in a sensitivity of 92% and a specificity of 96% to detect IS. A moderate correlation (rs = 0.73) between NR2 peptide values and acute ischemic cortical lesions (<200 mL) was found. Conclusions: This study suggests that the NR2 peptide may be a brain specific biomarker to diagnose acute IS and may allow the differentiation of IS from stroke mimics and controls. Additional larger scale clinical validation studies are required.

Original languageEnglish (US)
Article numbere42362
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 27 2012

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aspartic acid
N-Methyl-D-Aspartate Receptors
stroke
Assays
Stroke
Biomarkers
Peptides
assays
peptides
Brain
biomarkers
signs and symptoms (animals and humans)
peptide receptors
blood vessels
lesions (animal)
risk factors
Plasmas
Degradation
brain
Validation Studies

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dambinova, S. A., Bettermann, K., Glynn, T., Tews, M., Olson, D., Weissman, J. D., & Sowell, R. L. (2012). Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. PloS one, 7(7), [e42362]. https://doi.org/10.1371/journal.pone.0042362
Dambinova, Svetlana A. ; Bettermann, Kerstin ; Glynn, Theodore ; Tews, Matthew ; Olson, David ; Weissman, Joseph D. ; Sowell, Richard L. / Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. In: PloS one. 2012 ; Vol. 7, No. 7.
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abstract = "Background: The acute assessment of patients with suspected ischemic stroke remains challenging. The use of brain biomarker assays may improve the early diagnosis of ischemic stroke. The main goal of the study was to evaluate whether the NR2 peptide, a product of the proteolytic degradation of N-methyl-D-aspartate (NMDA) receptors, can differentiate acute ischemic stroke (IS) from stroke mimics and persons with vascular risk factors/healthy controls. A possible correlation between biomarker values and lesion sizes was investigated as the secondary objective. Methods and Findings: A total of 192 patients with suspected stroke who presented within 72 h of symptom onset were prospectively enrolled. The final diagnosis was determined based on clinical observations and radiological findings. Additionally gender- and age-matched healthy controls (n = 52) and persons with controlled vascular risk factors (n = 48) were recruited to compare NR2 peptide levels. Blinded plasma was assayed by rapid magnetic particles (MP) ELISA for NR2 peptide within 30 min and results for different groups compared using univariate and multivariate statistical analyses. There was a clinical diagnosis of IS in 101 of 192 (53{\%}) and non-stroke in 91 (47{\%}) subjects. The non-stroke group included presented with acute stroke symptoms who had no stroke (n = 71) and stroke mimics (n = 20). The highest NR2 peptide elevations where found in patients with IS that peaked at 12 h following symptom onset. When the biomarker cut off was set at 1.0 ug/L, this resulted in a sensitivity of 92{\%} and a specificity of 96{\%} to detect IS. A moderate correlation (rs = 0.73) between NR2 peptide values and acute ischemic cortical lesions (<200 mL) was found. Conclusions: This study suggests that the NR2 peptide may be a brain specific biomarker to diagnose acute IS and may allow the differentiation of IS from stroke mimics and controls. Additional larger scale clinical validation studies are required.",
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Dambinova, SA, Bettermann, K, Glynn, T, Tews, M, Olson, D, Weissman, JD & Sowell, RL 2012, 'Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke', PloS one, vol. 7, no. 7, e42362. https://doi.org/10.1371/journal.pone.0042362

Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. / Dambinova, Svetlana A.; Bettermann, Kerstin; Glynn, Theodore; Tews, Matthew; Olson, David; Weissman, Joseph D.; Sowell, Richard L.

In: PloS one, Vol. 7, No. 7, e42362, 27.07.2012.

Research output: Contribution to journalArticle

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T1 - Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke

AU - Dambinova, Svetlana A.

AU - Bettermann, Kerstin

AU - Glynn, Theodore

AU - Tews, Matthew

AU - Olson, David

AU - Weissman, Joseph D.

AU - Sowell, Richard L.

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