Article
The brainstem glioma model – neurological scoring, histological evaluation and MR imaging
Das Hirnstammgliom-Modell – neurologische Beurteilung, histologische Evaluation und MR Bildgebung
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Published: | May 30, 2008 |
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Objective: Diffuse brainstem gliomas account for 3 to15% of CNS tumors in children and are associated with fatal outcome. Convection enhanced delivery may be a promising option of treatment. We evaluate a brainstem tumor model in rats for local delivery with carboplatin using neurological scoring, histological evaluation and MR imaging.
Methods: In 60 male Fisher rats stereotactically 100,000 F-98 cells were implanted at 1.4mm lateral to midline and at the lambdoid suture using guided screws. After 4 days a cannula was implanted for local delivery connected to an AlzetTM pump (1μl/h over 7days) with either vehicle (5% dextrose) or low and high dose of carboplatin. All rats were subsequently tested neurologically using a specified neurological score. In 36 animals survival time was recorded. Representative MR imaging were acquired in 8 rats, respectively, at day 12 after tumor implantation. HE staining was used to evaluate tumor cell density and tumor volume.
Results: Neurological scoring showed significant higher impairment in the high dose carboplatin group during treatment period. Survival was significant prolonged compared to control animals in the high as well as in the low dose carboplatin groups (18.6±3 versus 26.3±9; 22.8±2 days; p<0.05). Overall neurological grading correlated with survival time. MR imaging showed a focal contrast enhancing mass in the pontine brainstem, which was less exaggerated after local chemotherapy. Histological slices visualized decreased cellular density in treatment animals versus controls.
Conclusions: Local chemotherapy in the brainstem glioma model showed significant efficacy for histological changes and survival. The neurological grading is important to evaluate drug and tumor related functional impairment during therapy.