Evaluation of blood-brain barrier permeability and the effect of interferon in mouse glioma model.
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 continuously cultured in vitro. Its proliferation was inhibited by homologous mouse interferon alpha/beta [MuIFN alpha/beta] but not by human interferon alpha lymphoblastoid or human interferon beta. The in vivo studies of G-26 glioma treatment with MuIFN alpha/beta 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.
D000818:Animals; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002199:Capillary Permeability; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006735:Horseradish Peroxidase; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009995:Osmosis
D005904:Glial Fibrillary Acidic Protein; D016898:Interferon-alpha; D007372:Interferons; D006735:Horseradish Peroxidase