Establishment of primary cell culture and an intracranial xenograft model of pediatric ependymoma: a prospect for therapy development and understanding of tumor biology.

BACKGROUND: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs. RESULTS: We elucidated the ultrastructure of the cultured EPN cells and characterized their profile of immunophenotypic pluripotency markers (CD133, CD90, SSEA-3, CXCR4). We established an experimental EPN model by the intracerebroventricular infusion of EPN cells labeled with multimodal iron oxide nanoparticles (MION), thereby generating a tumor and providing a clinically relevant animal model. MRI analysis was shown to be a valuable tool when combined with effective MION labeling techniques to accompany EPN growth. CONCLUSIONS: We demonstrated that GFAP/CD133+CD90+/CD44+ EPN cells maintained key histopathological and growth characteristics of the original patient tumor. The characterization of EPN cells and the experimental model could facilitate biological studies and preclinical drug screening for pediatric EPNs. METHODS: In this work, we established notoriously challenging primary cell culture of anaplastic EPNs (WHO grade III) localized in the posterior fossa (PF), using EPNs obtained from 1 to 10-year-old patients (n = 07), and then characterized their immunophenotype and ultrastructure to finally develop a xenograft model.

The Na+/K+ATPase activity is increased in the hippocampus after multiple status epilepticus induced by pilocarpine in developing rats.

The effects of repetitive pilocarpine-induced status epilepticus (SE) in the hippocampal Na(+)/K(+)ATPase activity were studied in developing rat. Na(+)/K(+)ATPase is a membrane-bound enzyme responsible for the active transport of sodium and potassium ions through the membrane. It is necessary to maintain neuronal excitability. The malfunction of this enzyme has been associated with neuronal hyperexcitability. The pilocarpine-induced status epilepticus in developing rats leads to neuronal hyperexcitability and brain damage. We examined the activity of the Na(+)/K(+)ATPase enzyme in hippocampus of rats submitted to 1 episode of status epilepticus on postnatal day 9 and to 3 episodes of pilocarpine-induced status epilepticus on postnatal days 7, 8 and 9. Our findings showed that one status epilepticus episode does not modify the Na(+)/K(+)ATPase activity in hippocampus of rats studied 7 or 30 days later (at P16 or P39). However, an increase in the Na(+)/K(+)ATPase activity was detected in hippocampus of rats submitted to three consecutive status epilepticus during the development studied 7 (+142%) and 30 (+400%) days following the injections. In addition, a significant reduction in the Na(+)/K(+)ATPase activity was observed in control rats at P39 compared to P16. Our data suggest that multiple pilocarpine-induced status epilepticus in developing rats induce long-lasting increase in the Na(+)/K(+)ATPase activity in the hippocampus, reflecting hyperexcitability.