A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest

Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop an assay detecting the neo-epitope generated by caspase-6 cleavage of GFAP (GFAP-C6), and to assess the ability of GFAP-C6 to reflect pathological processes in patients suffering a cardiac arrest and subsequent global cerebral ischemia. Anti-GFAP-C6 antibodies recognized their specific target sequence, and dilution and spike recoveries in serum were within limits of ±20% reflecting high precision and accuracy of measurements. Intra- and inter-assay CVs were below limits of 10% and 15%, respectively. Serological levels of GFAP-C6 were significantly elevated 72 hours after CA (Mean±SD) (20.39±10.59 ng/mL) compared to time of admission (17.79±10.77 ng/mL, p