Erythropoietin in the cerebrospinal fluid of patients with aneurysmal subarachnoid haemorrhage originates from the brain

Recent years’ research has revealed a specific, neuroprotective erythropoietin (EPO) system in the central nervous system (CNS) that is upregulated by hypoxia. The presence and dynamics of EPO in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH) has not been investigated. We collected a total of 83 corresponding serum and CSF samples from 18 patients with aneurysmal SAH and compared the concentrations of EPO with those of blood-derived markers of blood–brain barrier function (albumin, transferrin, α2-macroglobulin) and with those of proteins with well-known CNS synthesis (prealbumin, apolipoprotein E). The EPO concentration in CSF was 0.93 (0.82) mU/ml (median and inter-quartile range). Nine patients presented CSF-EPO values above 1 mU/ml. CSF levels did not correlate with serum concentrations and were independent of blood–brain barrier integrity suggesting a synthesis in CNS rather than a blood-derived origin. Furthermore, the median CSF:serum ratio (Qprotein) of EPO was similar to those of prealbumin and apolipoprotein E, and much higher than those of albumin, transferrin and α2-macroglobulin. When the Qprotein of all proteins were plotted against Qalbumin, EPO showed dynamics similar to CNS-derived proteins. Our data indicate that EPO in the CSF of patients with aneurysmal SAH originates mainly from the CNS.