Influence of deferoxamine on hydrocephalus after intraventricular hemorrhage and expressions of Wnt1 and Wnt3a in rat

Abstract

Objective To observe the effect of deferoxamine on chronic hydrocephalus after intraventricular hemorrhage (IVH) and the role of Wnt (Wnt1 and Wnt3a).Methods A total of 130 Sprague Dawley male rats were randomly assigned into 4 groups:normal control group,sham- IVH group,IVH group and deferoxamine -treated group.The rats of subgroups except normal control group received an injection of autologous blood or saline into right lateral cerebral ventricles.Deferoxamine or vehicle was administered 3 hours after IVH and then every 12 hours up to 7 days in IVH group and deferoxamine -treated group.Rats were euthanized at 1,7,28 days for measurement,and the transverse diameter of the lateral ventricles were observed for evaluation of hydrocephalus.The expression of Wntl and Wnt3a were measured by RT - PCR and Western Blot.Results At 28 days,there was no hydrocephalus in the normal control group and sham - IVH group.80 ％ (12/15) of the rats in IVH group developed hydrocephalus.The rate was only 20 ％ (3/15) in deferoxamine - treated group,which was much lower than that in IVH group.The expression of Wnt1 mRNA was normal in normal control group and shame -IVH group,and up-regulated in IVH group.The peak expression was detected at 28 days.The expression was significantly higher than that in shame - IVH group at 7 days and 28 days,after deferoxamine treatment,downregnlation of Wnt1 mRNA were observed and were significantly lower than that in IVH group.The Wnt3a mRNA had similar trends,while the expressed level was normal in normal control group and shame - IVH group,and up -regulated following IVH.The peak expression was detected at 28 days,and was significantly higher than that in shame - IVH group at 7 days and 28 days.After deferoxamine treatment,the downregulation of Wnt3a mRNA was observed and was significantly lower than that in IVH group.Accordingly,Wntl protein expression was normal in normal control group and shame - IVH group,and increased after IVH.At 7 days and 28 days,the Wnt1 protein expression of IVH group was markedly higher than shame - IVH group.After deferoxamine treatment,the expression of Wnt1 protein was reduced and significantly lower than that of IVH group.The expression of Wnt3a protein was also normal in normal control group and shame - IVH group.The up - regulation of the protein expression was observed following IVH at 28 days,while down - regulation was observed after deferoxamine treatment at 28 days.Conclusions Deferoxamine could reduce hydrocephalus after IVH,and Wnt pathway may play an important role in the development of IVH and therapeutic effect of deferoxamine. Key words: Hydrocephalus ; Intraventricular hemorrhage ; The Wnt signaling pathway ; Deferoxamine ;