Abstract
Objective
Brainstem tumor models are required to advance the treatment for diffuse pontine gliomas in children. The feasibility of creating an experimental rodent model by inoculating newborn pups with tumor cells was examined. The study was performed to create an animal model for diffuse brainstem tumors.
Methods
Eighty-two Fischer rat pups aged 12–24 h were anesthetized by hypothermia. The brainstem was injected with saline to identify anatomical coordinates for subsequent tumor cell challenges. The newborn pups were then inoculated with F98 (n=30) or 9L (n=30) glioma cells. Animals were returned to their mother for nursing. Tumor growth was assessed by survival and histopathology.
Results
Twenty-one percent of the saline-treated animals (17 out of 82) and 5% of the tumor cell-challenged pups (3 out of 60) were eliminated by their mothers. Inoculations with 9L and F98 cells produced brainstem tumors in 83% (24 out of 29) and 93% of animals (26 out of 28) respectively that were evaluated.
Conclusions
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abbott R, Goh KYC (1999) Brainstem gliomas. In: Albright L, Pollack I, Adelson D (eds) Principles and practices of pediatric neurosurgery. Thieme, New York, pp 629–640
Carson BSS, Guarnieri M (2002) Local therapy for brain tumors. Adv Clin Neurosci 12:89–99
Fisher PG, Carson BS (1996) Management of brainstem gliomas in children. Contemp Neurosurg 18:1–7
Groothuis DR (2000) The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neurooncology 2:45–59
Klopp LS, Simpson ST, Sorjonen DC, Lenz SD (2000) Ventral surgical approach to the caudal brain stem in dogs. Vet Surg 29:533–542
Occhiogrosso G, Edgar MA, Sandberg DI, Souweidane MM (2003) Prolonged convection-enhanced delivery into the rat brainstem. Neurosurgery 52:388–394
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, Orlando
Peterson DL, Sheridan PJ, Brown WEJ (1994) Animal models for brain tumors: historical perspectives and future directions. J Neurosurg 80:865–876
Sandberg DI, Edgar MA, Souweidane MM (2002) Convection-enhanced delivery into the rat brainstem. J Neurosurg 96:885–891
Tamargo RJ, Epstein JI, Brem H (1988) Heterotransplantation of malignant human gliomas in neonatal rats. J Neurosurgery 69:928–933
Wetmore C, Eberhart DE, Curran T (2001) Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res 61:513–516
Wu Q, Tyler B, Sukay L, Rhines L, DiMeco F, Clatterbuck RE, Guarnieri M, Carson BS Sr (2002) Experimental rodent models of brainstem tumors. Vet Pathol 39:293–299
Xiao A, Wu H, Pandolfi PP, Louis DN, VanDyke T (2002) Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell 1:157–168
Acknowledgements
This work was supported by funds from the Children’s Cancer Foundation, Baltimore, MD, USA.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jallo, G.I., Penno, M., Sukay, L. et al. Experimental models of brainstem tumors: development of a neonatal rat model. Childs Nerv Syst 21, 399–403 (2005). https://doi.org/10.1007/s00381-004-1100-6
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00381-004-1100-6