Growth Factors and the Choroid Plexus: Their Role in Posthemorrhagic Hydrocephalus

Background/Objectives: Intraventricular hemorrhage (IVH) frequently occurs in premature infants and adults with intracerebral or subarachnoid hemorrhage. It is a major cause of cerebral palsy in premature infants and a risk factor for poor outcome in adult cerebral hemorrhage. Posthemorrhagic hydrocephalus is a common complication of IVH and aggravates brain damage. Hemoglobin (Hb), released from the hemorrhage after IVH, has been implicated in IVH-induced hydrocephalus. The aim of the current study was to examine the impact of Hb on the choroid plexuses (CPs) that reside in the ventricular system. Methods: Experiments were performed in freshly isolated CPs, in primary cultures of CP epithelial cells (CPECs), and in the Z310 cell line exposed to Hb with MTT assay, scratch wound healing assay, cell counting/total cell protein measurement and RT-qPCR. Results: We found that Hb significantly induced CPEC proliferation (e.g., 37-65% higher than control by MTT assay and 56% higher than control by cell counting), and upregulated mRNA expression of growth factors in isolated CP tissue (e.g., IGF-2 and NGF were 39% and 79% higher than control by RT-PCR). Hb also remarkably induced mRNA expression of NKCC1 (50%) and claudin-2 (154%), two proteins involved in CSF secretion, in isolated CP tissue. Conclusions: These results indicate that Hb-induced growth factor-mediated CP proliferation and upregulation of CSF secretion-related proteins might contribute to PHH and suggest there may be alternate therapeutic targets for PHH.