title: Serum neurogranin measurement as a biomarker of acute traumatic brain injury.
abstract: OBJECTIVE
  Neurogranin (NRGN) is a small neuronal protein that plays an important role in synaptic signaling by regulating calmodulin (CaM) availability. In this study, we developed an ELISA to measure NRGN quantitatively in serum samples from a cohort of acute traumatic brain injury (TBI) patients and a non-TBI control cohort, and explored the potential value of NRGN as a circulating biomarker for TBI.
  
  
  METHODS
  Recombinant His-NRGN protein was used to develop mouse monoclonal capture and rabbit polyclonal detection antibodies, and they were used to develop a sandwich ELISA. After validation, we used this ELISA to measure serum samples from a cohort of typical adult acute TBI patients (N=76 TBI cases) and non-TBI control patients (N=150 controls).
  
  
  RESULTS
  The NRGN ELISA lower limit of detection was 0.055ng/mL, lower limit of quantification was 0.2ng/mL, and interassay CVs were ≤10.7%. The average recovery was 99.9% (range from 97.2-102%). Serum NRGN concentrations in TBI cases were significantly higher than in controls (median values were 0.18ng/mL vs. 0.02ng/mL, p<0.0001), but did not discriminate TBI cases with intracranial hemorrhage (p=0.09).
  
  
  CONCLUSIONS
  We have developed a highly sensitive and reproducible ELISA for measuring circulating NRGN in blood samples. Serum NRGN concentrations in acute TBI patients were significantly higher than in controls, indicating that NRGN could have utility as a circulating biomarker for acute TBI. This report provides evidence to support larger and controlled TBI clinical studies for NRGN validation and prediction of outcomes.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.
authors.forename: Frederick K
authors.initials: FK
authors.lastname: Korley
authors.affiliation: Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University, School of Medicine, Baltimore, MD, United States. Electronic address: aeveret3@jhmi.edu.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Everett
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood*; D016022:Case-Control Studies; D003710:Demography; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051579:Neurogranin / Q000097:blood*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D011994:Recombinant Proteins; D051579:Neurogranin
keywords: Biomarker; ELISA; Neurogranin; Traumatic brain injury