High Thrombopoietin Concentrations in The Cerebrospinal Fluid of Neonates with Sepsis And Intraventricular Hemorrhage May Contribute to Brain Damage.

Thrombopoietin (TPO) and its receptor (TPOR) are expressed in the central nervous system (CNS). Although TPO shares significant homology with various neurotrophins, recent data indicate a proapoptotic function of TPO in the CNS. In this study, TPO concentrations were analyzed in the cerebrospinal fluid (CSF) of neonates. Human neuroblastoma-derived SH-SY5Y cells were established to elucidate the effects of inflammation and hypoxia on neuronal Tpoexpression. TPO was detectable in the CSF of 6 of 15 neonates with bacterial infectionsepsis (median 140, range 2–613 pgmL), 5 of 9 neonates with posthemorrhagic hydrocephalus (median 31, range 1.4–469 pgmL), 3 of 4 neonates with posthemorrhagic hydrocephalus plus bacterial infectionsepsis or meningitis (median 97, range 6–397 pgmL), but not in controls ( n 3). Neither the presence of detectable TPO nor its level in the CSF significantly correlated with any clinical or laboratory parameter. In SH-SY5Y cells, TPO and TPOR expression was detected by RT-PCR and Western blot analysis. In vitro, interleukin-6 (IL-6) did not significantly change Tpogene expression. In contrast, TpomRNA expression significantly decreased under hypoxia, whereas erythropoietin (EPO) mRNA expression increased. In conclusion, our data provide evidence that in neuronal cells, TPO production is regulated by different mechanisms than in hepatocytes. [ABSTRACT FROM AUTHOR]