Erythropoietin in the cerebrospinal fluid of neonates who sustained CNS injury

We previously reported that erythropoietin (Epo) is present in human cerebr ospinal fluid (CSF). It is not known whether CSF Epo concentrations change under conditions of CNS injury or, if so, whether this change reflects loss of blood-brain barrier integrity or increased CNS Epo synthesis. We hypoth esized that CSF Epo increases in conditions of neural injury including hypo xia, meningitis, and intraventricular hemorrhage (IVH) and that CSF Epo con centrations are independent of plasma Epo concentrations. To test these hyp otheses, Epo concentrations were measured in 122 paired CSF and blood sampl es obtained from neonates and children categorized as follows: 16, asphyxia ; 31, meningitis; Il, IVH; 41, controls. Twelve infants treated with recomb inant Epo (rEpo) and 11 additional samples from children with miscellaneous neurologic problems were also evaluated. CSF and plasma Epo concentrations were significantly higher in asphyxiated infants than in controls (225.0 /- 155.0 versus 4.5 +/- 0.5 mU/mL; mean +/- SEM, p < 0.05, respectively, in CSF; 1806.7 +/- 1254 versus 5.2 +/- 0.5, p < 0.05 in plasma). Neonates wit h IVH had higher CSF Epo concentrations than controls (p < 0.01) but did no t have higher plasma Epo concentrations than controls. Patients with mening itis did not have elevated CSF or plasma Epo concentrations. There was no c orrelation between CSF and plasma Epo concentrations in infants treated wit h rEpo. We conclude that Epo is selectively increased in the CSF by hypoxia , less so by IVH, and not at all by meningitis. rEpo treatment does not ele vate CSF Epo. These findings suggest that rEpo does not cross the blood-bra in barrier and that hypoxia induces increased CNS synthesis of Epo.