A novel method of intracranial injection via the postglenoid foramen for brain tumor mouse models

Laboratory investigation

Kenichiro Iwami M.D., Hiroyuki Momota M.D., Ph.D., Atsushi Natsume M.D., Ph.D., Sayano Kinjo B.S., Tetsuya Nagatani M.D., Ph.D., and Toshihiko Wakabayashi M.D., Ph.D.
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  • Department of Neurosurgery, Nagoya University, Graduate School of Medicine, Nagoya, Japan
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Object

Mouse models have been widely used in developing therapies for human brain tumors. However, surgical techniques such as bone drilling and skin suturing to create brain tumors in adult mice are still complicated. The aim of this study was to establish a simple and accurate method for intracranial injection of cells or other materials into mice.

Methods

The authors performed micro CT scans and skull dissection to assess the anatomical characteristics of the mouse postglenoid foramen. They then used xenograft and genetically engineered mouse models to evaluate a novel technique of percutaneous intracranial injection via the postglenoid foramen. They injected green fluorescent protein–labeled U87MG cells or virus-producing cells into adult mouse brains via the postglenoid foramen and identified the location of the created tumors by using bioluminescence imaging and histological analysis.

Results

The postglenoid foramen was found to be a well-conserved anatomical structure that allows percutaneous injection into the cerebrum, cerebellum, brainstem, and basal cistern in mice. The mean (± SD) time for the postglenoid foramen injection technique was 88 ± 15 seconds. The incidence of in-target tumor formation in the xenograft model ranged from 80% to 100%, depending on the target site. High-grade gliomas were successfully developed by postglenoid foramen injection in the adult genetically engineered mouse using virus-mediated platelet-derived growth factor B gene transfer. There were no procedure-related complications.

Conclusions

The postglenoid foramen can be used as a needle entry site into the brain of the adult mouse. Postglenoid foramen injection is a less invasive, safe, precise, and rapid method of implanting cells into the adult mouse brain. This method can be applied to both orthotopic xenograft and genetically engineered mouse models and may have further applications in mice for the development of therapies for human brain tumors.

Abbreviations used in this paper: GFP = green fluorescent protein; PDGFB = platelet-derived growth factor B; RCAS = replication-competent avian leukosis virus splice acceptor.

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Contributor Notes

Address correspondence to: Hiroyuki Momota, M.D., Ph.D., Department of Neurosurgery, Nagoya University, Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. email: momota@med.nagoya-u.ac.jp.

Please include this information when citing this paper: published online December 9, 2011; DOI: 10.3171/2011.10.JNS11852.

  • 1

    Barnabé-Heider F, , Meletis K, , Eriksson M, , Bergmann O, , Sabelström H, & Harvey MA, : Genetic manipulation of adult mouse neurogenic niches by in vivo electroporation. Nat Methods 5:189196, 2008

    • Search Google Scholar
    • Export Citation
  • 2

    Boyd GI: The emissary foramina of the cranium in primates. J Anat 69:113117, 1934

  • 3

    Brennan C, , Momota H, , Hambardzumyan D, , Ozawa T, , Tandon A, & Pedraza A, : Glioblastoma subclasses can be defined by activity among signal transduction pathways and associated genomic alterations. PLoS One 4:e7752, 2009

    • Search Google Scholar
    • Export Citation
  • 4

    Butler H: The development of mammalian dural venous sinuses with especial reference to the post-glenoid vein. J Anat 102:3356, 1967

  • 5

    Chamberlain MC: Radiographic patterns of relapse in glioblastoma. J Neurooncol 101:319323, 2011

  • 6

    Dai C, , Celestino JC, , Okada Y, , Louis DN, , Fuller GN, & Holland EC: PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 15:19131925, 2001

    • Search Google Scholar
    • Export Citation
  • 7

    de Vries NA, , Bruggeman SW, , Hulsman D, , de Vries HI, , Zevenhoven J, & Buckle T, : Rapid and robust transgenic high-grade glioma mouse models for therapy intervention studies. Clin Cancer Res 16:34313441, 2010

    • Search Google Scholar
    • Export Citation
  • 8

    Fomchenko EI, & Holland EC: Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res 12:52885297, 2006

    • Search Google Scholar
    • Export Citation
  • 9

    Hambardzumyan D, , Amankulor NM, , Helmy KY, , Becher OJ, & Holland EC: Modeling adult gliomas using RCAS/t-va technology. Transl Oncol 2:8995, 2009

    • Search Google Scholar
    • Export Citation
  • 10

    Holland EC, , Hively WP, , DePinho RA, & Varmus HE: A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev 12:36753685, 1998

    • Search Google Scholar
    • Export Citation
  • 11

    Maroldi R, , Ambrosi C, & Farina D: Metastatic disease of the brain: extra-axial metastases (skull, dura, leptomeningeal) and tumour spread. Eur Radiol 15:617626, 2005

    • Search Google Scholar
    • Export Citation
  • 12

    Ozawa T, & James CD: Establishing intracranial brain tumor xenografts with subsequent analysis of tumor growth and response to therapy using bioluminescence imaging. J Vis Exp 41:e1986, 2010

    • Search Google Scholar
    • Export Citation
  • 13

    Padget DH: The cranial venous system in man in reference to development, adult configuration, and relation to the arteries. Am J Anat 98:307355, 1956

    • Search Google Scholar
    • Export Citation
  • 14

    Paugh BS, , Qu C, , Jones C, , Liu Z, , Adamowicz-Brice M, & Zhang J, : Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol 28:30613068, 2010

    • Search Google Scholar
    • Export Citation
  • 15

    Phillips HS, , Kharbanda S, , Chen R, , Forrest WF, , Soriano RH, & Wu TD, : Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157173, 2006

    • Search Google Scholar
    • Export Citation
  • 16

    Piette E, & Lametschwandtner A: The fine vasculature of the rat mandibular joint. Acta Anat (Basel) 153:6472, 1995

  • 17

    Ragel BT, , Elam IL, , Gillespie DL, , Flynn JR, , Kelly DA, & Mabey D, : A novel model of intracranial meningioma in mice using luciferase-expressing meningioma cells. Laboratory investigation. J Neurosurg 108:304310, 2008

    • Search Google Scholar
    • Export Citation
  • 18

    Rood BR, & MacDonald TJ: Pediatric high-grade glioma: molecular genetic clues for innovative therapeutic approaches. J Neurooncol 75:267272, 2005

    • Search Google Scholar
    • Export Citation
  • 19

    Shih AH, , Dai C, , Hu X, , Rosenblum MK, , Koutcher JA, & Holland EC: Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis. Cancer Res 64:47834789, 2004

    • Search Google Scholar
    • Export Citation
  • 20

    Stupp R, , Mason WP, , van den Bent MJ, , Weller M, , Fisher B, & Taphoorn MJ, : Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987996, 2005

    • Search Google Scholar
    • Export Citation
  • 21

    Wen PY, & Kesari S: Malignant gliomas in adults. N Engl J Med 359:492507, 2008

  • 22

    Wysocki J: Morphology of the temporal canal and postglenoid foramen with reference to the size of the jugular foramen in man and selected species of animals. Folia Morphol (Warsz) 61:199208, 2002

    • Search Google Scholar
    • Export Citation
  • 23

    Yi D, , Hua TX, & Lin HY: EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice. Cancer Invest 29:229239, 2011

    • Search Google Scholar
    • Export Citation

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