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A novel brainstem tumor model: functional and histopathological characterization

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Abstract

Introduction

Diffuse pontine gliomas remain a challenging and frustrating disease to treat. The survival rates for these high-grade brainstem tumors (BSTs) is dismal and optimal therapy has yet to be determined. The development of a satisfactory brainstem tumor model is necessary for testing new therapeutic paradigms that may prolong survival.

Materials and methods

We report the surgical technique, functional testing, and histopathological features of a novel brainstem tumor model in rats. Female Fischer 344 rats (n=45) were randomized to receive an injection of either 3 μl of 9L gliosarcoma cells (100,000 cells, n=), 3 μl of F98 glioma cells (100,000 cells, n=10), or 3 μl of medium (Dulbecco’s modified eagle medium) into the pontine tegmentum. Using a cannulated guide screw system, implanted in the skull of the animal, we injected each group at coordinates 1.4 mm right of the sagittal and 1.0 mm anterior of the lambdoid sutures, at a depth of 7.0 mm from the dura. The head was positioned 5° from horizontal before injection. The rats were post-operatively evaluated for neurological deficits using an automated test. Kaplan–Meier curves were generated for survival and disease progression, and brains were processed postmortem for histopathology.

Results and discussion

9L and F98 tumor cells grew in 100% of animals injected and resulted in a statistically significant mean onset of hemiparesis of 16.5±0.56 days (P=0.001, log-rank test), compared to animals in the control group which lacked neurological deficits by day 60. The animals with tumor cells implanted demonstrated significant deterioration of function on the automated rod testing. Animals in the control group showed no functional or pathological signs of tumor. Progression to hemiparesis was consistent in all tumor-injected animals, with predictable onset of symptoms occurring approximately 17 days post-surgery. The histopathological characteristics of the 9L and F98 BSTs were comparable to those of aggressive human BSTs.

Conclusion

The establishment of this animal tumor model will facilitate the testing of new therapeutic paradigms for the treatment of BSTs.

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Acknowledgements

We would like to thank Norman Barker for histology and Ian Suk for his wonderful illustrations.

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Authors and Affiliations

  1. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    George I. Jallo, Andrey Volkov, Cyrus Wong & Benjamin S. Carson Sr.

  2. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    George I. Jallo & Benjamin S. Carson Sr.

  3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    George I. Jallo & Benjamin S. Carson Sr.

  4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Margaret B. Penno

  5. Division of Pediatric Neurosurgery, Johns Hopkins Hospital, Harvey 811, 600 North Wolfe Street, Baltimore, MD, 21287, USA

    George I. Jallo

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  1. George I. Jallo
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  2. Andrey Volkov
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  3. Cyrus Wong
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  4. Benjamin S. Carson Sr.
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  5. Margaret B. Penno
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Correspondence to George I. Jallo.

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Jallo, G.I., Volkov, A., Wong, C. et al. A novel brainstem tumor model: functional and histopathological characterization. Childs Nerv Syst 22, 1519–1525 (2006). https://doi.org/10.1007/s00381-006-0174-8

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  • DOI: https://doi.org/10.1007/s00381-006-0174-8

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