Morphometrical characterization of two glioma models in the brain of immunocompetent and immunodeficient rats

Abstract

Although several glioma models exist, systematic morphometrical studies on such experimental tumors are lacking. The purpose of this study was the quantitative assessment of how rat strains, cell lines, injection techniques and location affect tumors reproducibility and histopathological features. Glioma cells were implanted in 3 brain locations, with different injection techniques (free hand, stereotactic, water-tight device), variable volumes, cell concentrations and infusion rates. Tumors were developed from 2 rat glioma cell lines (9L and C6) in immunocompetent (Wistar and Fischer 344) and immunodeficient rats (New Zealand). Animals underwent daily neurological examination. At the scheduled time the tumors were macro and microscopically evaluated and a quantitative morphometrical analysis was performed. C6 gliomas appeared very infiltrative and irregularly shaped; 9L gliomas showed, by using the same injection technique, a grossly regular shape. Margins at the tumor-brain interface were macroscopically demarcated in the immunocompetent rats. In the nude rats, 9L tumors appeared microscopically more infiltrative, although regularly shaped, with a closer morphological resemblance to human gliomas. The implantation in the frontal area, anterior to the nucleus caudatus (3 mm anterior the coronal suture) gave reproducible tumor shape and size, no hydrocephalus and no early neurological deterioration. The use of a stereotactic technique or of a water-tight device, small volume (< 10 microl) of cell suspension, low infusion rate were useful to reduce morbidity and to improve data reproducibility. No difference in morbidity and mortality were observed in immunocompetent and immunodeficient rats. The 9L glioma model with stereotactic implantation constitutes a good option for reliable morphometrical evaluation of tumor growth. We propose a location for tumor implantation anterior to the nucleus caudatus. This produced the longest symptom-free survival.