Evaluation of blood-brain barrier permeability and the effect of interferon in mouse glioma model

Summary The aim of this study was to evaluate whether interferon [IFN] can affect intracerebrally grown glioma and how alteration of the blood-brain barrier [BBB] may influence this effect. An intracerebrally implanted glioma G-26 (G-26) mouse brain-tumor model was developed and used in these studies. Histological characterization of this intracerebrally grown tumor revealed its anaplastic character. The astrocytic origin of G-26 was evidenced by glial fibrillary acidic protein staining and electron microscopic visualization of glial filaments. A study of tumor progression and animal survival showed development of a well defined tumor nodule within approximately seven days after the implantation. The median animal survival time was 27 ±3.8 days. The integrity of the blood-brain barrier [BBB] within the tumor was evaluated by the intravenous injection of horseradish peroxidase at days 3, 7,10 and 20 after brain tumor implant and compared to sham controls. The tumor-induced BBB alteration was progressive from day 3 to day 20.Glioma-26 subcutaneously passed in C57BL/6 mice was also continously cultured in vitro. Its proliferation was inhibited by homologous mouse interferon / [MuIFN / but not by human interferon a lymphoblastoid or human interferon ß. The in vivo studies of G-26 glioma treatment with MuIFN / were performed using single bolus of IFN in osmotically altered animals or slow IFN infusion through osmotic micro-pumps. The slow infusion of IFN had no effect on animal survival. However, a statistically significant increase in animal survival was observed after single bolus IFN treatment following osmotic BBB alteration.