New xenograft model for assessing experimental therapy of central nervous system tumors: Human glioblastoma in the intrathecal compartment of the nude mouse

Chad D. Abernathey, Kimberly L. Kooistra, George L. Wilcox, Edward R. Laws

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Ten congenitally athymic “nude” mice and 10 immunocompetent mice underwent intrathecal inoculation with a human glioblastoma cell line (U87MG) via percutaneous lumbar puncture (5 × 105 cells/animal). All of the nude mice developed paraplegia with or without incontinence at 2 weeks and routinely died of inanition 3 weeks postimplantation. Histological examination confirmed extensive proliferation of neoplastic cells within the intrathecal space. A second group of animals was inoculated with 5 × 104 cells/animal: 20 nude mice, 10 cyclosporine A-immunosuppressed animals, and 10 immunocompetent control mice. The 20 mice were further divided into four subsets. Subset A did not receive chemotherapy, Subset B received 200 mg of carmustine (BCNU) per m2 by intraperitoneal injection, Subset C received a single dose of 4 mg of methotrexate (MTX) per m2 by intrathecal injection 4 hours after tumor inoculation, and Subset D received 12 mg of intrathecal MTX per m2. Decreasing the concentration of cells per animal by 1 log doubled the time interval required for the development of paralysis and incontinence to 4 weeks. Treatment with intrathecal MTX at a dose of 4 mg/m2 extended the symptom-free period by an additional week (to 5 weeks postinoculation), and a dose of 12 mg/m2 allowed an average of 6 weeks before the onset of neurological impairment. The xenografts did not grow in the immunocompetent control mice, the BCNU-treated group, or the cyclosporine A-immunosuppressed animals. An intrathecal xenograft model of central nervous system malignancies allows a novel approach to the evaluation of experimental chemotherapy. Direct interactions among the xenograft, the central nervous system, and the antineoplastic agents are accurately assessed clinically and histologically in an in vivo environment.

Original languageEnglish (US)
Pages (from-to)877-881
Number of pages5
JournalNeurosurgery
Volume22
Issue number5
DOIs
StatePublished - May 1988

Keywords

  • Chemotherapy
  • Glioblastoma
  • Nude mouse
  • Tumor model
  • Xenograft

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