C-type natriuretic peptide (CNP) is a paracrine growth factor regulating cell proliferation and maturation in many tissues including the brain and spinal cord1. Consistent with high abundance in CNS tissue, concentrations of CNP and a bio-inactive fragment of the propeptide (aminoterminal proCNP, NTproCNP) are respectively 3-20 fold higher in cerebrospinal fluid (CSF) than those in the systemic circulation. As well as promoting neurogenesis and connectivity,2-3 recent reports show that intracerebroventricular administration of CNP reduces food intake in rodents4. Whether CNP forms in plasma can affect CSF concentrations is unknown but important to address now that treatment using systemic administration of CNP agonists is planned for children with disorders of skeletal growth5. Accordingly we have measured CNP forms in time-matched samples of CSF and plasma in pregnant sheep – a physiologically unique setting in which plasma concentrations of CNP forms are markedly increased for prolonged periods6. Concomitant samples of CSF and plasma were collected from twin bearing ewes (n = 15) throughout gestation and from 15 non pregnant control ewes. As shown in the table, much higher concentrations of NTproCNP and CNP were observed in CSF compared with plasma in non pregnant ewes. Despite marked increases in both CNP forms in plasma during pregnancy, there was no significant increase in the CSF concentration of either peptide.
In conclusion, sustained high concentrations of CNP forms in the systemic circulation do not affect CSF levels. As well as providing evidence that CNP is differentially regulated across the brain in normal health, our findings indicate that restricted entry from plasma to CSF is maintained during pregnancy.