Our results demonstrate that neonatal rat models for brainstem tumors can be prepared using known injection coordinates and orthotopic cell lines. Decreasing rates of maternal removal during the course of the work suggests that the method involves a learning curve.

Abstract. Despite recent advances in surgical technology, resection is not an option for many brainstem tumors. Experimental models have played essential roles in examining new approaches to therapy. The objective of the present study was to generate models by determining coordinates for safe inoculation into the brainstem of mice and rats, and to establish whether the implantation of heterotopic cells would create reproducible survival curves. Morbidity and survival studies were used to map stereotactic coordinates allowing successful inoculation of tumor cells. Survival studies were used to investigate the time course of tumor growth. Tumor location was examined by light microscopy and magnetic resonance imaging. Mice survived injections of 2 L of saline at interaural, lateral, and depth coordinates of Ϫ2.5, 1.0, and 3.5 mm and Ϫ1.5, 1.0, and 3.5 mm. Rats survived injections at interaural, lateral, and depth coordinates of Ϫ2.0, 2.0, and 7.0 mm and Ϫ3.0, 0, and 7.0 mm. Median survival of mice challenged with 5 ϫ 10 5 EMT6 and 10 4 B16 tumor cells was 11 and 10 days, respectively. Median survival for rats challenged with 10 4 9L and F98 cells was 14 and 13 days, respectively. The present study demonstrates a feasible approach to preparing models of brainstem tumors. Limitations of these models are discussed.

Because the brainstem has little functional redundancy, diffuse lesions have been regarded as inoperable. To determine whether local drug therapy can prolong survival in a rodent model of a tumor in such eloquent tissue, lethal doses of F98 and 9L tumor cells were injected into the brainstems of Fischer 344 rats. Five days after inoculations, 0.5 mg/ml solutions of carboplatin were infused at 1 microl/h for 7 days. Compared to control groups that survived 13-17 days with F98 tumors and 22-23 days with 9L tumors, animals locally infused with 0.1 mg of carboplatin survived 27-30 days (Prob > Chi Sq = 0.0003), and 32 days (Prob > Chi Sq = 0.01), respectively. Measurements of tissue platinum levels at autopsy suggested that infusions distributed pharmacologically relevant levels of carboplatin through a volume of tissue at least 0.5 cm in diameter. The results suggest that chronic low-flow infusions provide a promising approach to therapy for CNS lesions in tissues considered to be inoperable.