GFAP and antibodies against NMDA receptor subunit NR2 as biomarkers for acute cerebrovascular diseases

J Cell Mol Med. 2015 Sep;19(9):2253-61. doi: 10.1111/jcmm.12614. Epub 2015 Jun 17.


We studied whether the serum levels of glial fibrillary acidic protein (GFAP) and of antibodies against the N-methyl-d-aspartate receptor subunit NR2 (NR2 RNMDA ) can discriminate between intracerebral haemorrhage (ICH) and ischaemic stroke (IS) in stroke patients. We prospectively recruited patients with suspected stroke (72 confirmed) and 52 healthy controls. The type of brain lesion (ICH or IS) was established using brain imaging. The levels of GFAP and of antibodies against NR2 RNMDA were measured in blood samples obtained within 12 hrs after stroke onset and 24, 48 and 72 hrs and 1 and 2 weeks later using ELISA immunoassay. Improvement in diagnostic performance was assessed in logistic regression models designed to predict the diagnosis and the type of stroke. GFAP peaks early during haemorrhagic brain lesions (at significantly higher levels), and late in ischaemic events, whereas antibodies against NR2 RNMDA have significantly higher levels during IS at all time-points. Neither of the two biomarkers used on its own could sufficiently discriminate patients, but when they are used in combination they can differentiate at 12 hrs after stroke, between ischaemic and haemorrhagic stroke with a sensitivity and specificity of 94% and 91%, respectively.

Keywords: GFAP; NMDA; intracerebral haemorrhage; ischaemic stroke; neuronal biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Antibodies / metabolism*
  • Biomarkers / metabolism
  • Cerebrovascular Disorders / metabolism*
  • Female
  • Glial Fibrillary Acidic Protein / metabolism*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Protein Subunits / metabolism*
  • ROC Curve
  • Receptors, N-Methyl-D-Aspartate / immunology*
  • Stroke / metabolism


  • Antibodies
  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • NR2A NMDA receptor
  • Protein Subunits
  • Receptors, N-Methyl-D-Aspartate