The effects of temozolomide delivered by prolonged intracerebral microinfusion against the rat brainstem GBM allograft model

Junichi Yoshimura, I. Mei Siu, Ulrich W. Thomale, George I. Jallo

Research output: Contribution to journalArticle

Abstract

Objective: Diffuse intrinsic brainstem gliomas are considered to be inoperable. We report our initial experience of temozolomide (TMZ) administration into brainstem by intracerebral (i.c.) microinfusion using a rat brainstem glioblastoma allograft model. Methods: Forty-eight Fischer 344 female rats were used. In a feasibility study, various doses of i.c.-TMZ (1-10 mg) were administered into the brainstem using AlzetTM pumps in order to evaluate survival rates and neurotoxicity. For tumor implantation, rats received an injection of 105 9 L gliosarcoma cells. For local therapy, 5 days after inoculation, a total amount of 1 mg of TMZ or saline was administered into the brainstem at 1 μl/h over 7 days (n=8/group). For systemic therapy, rats were treated with an orally administered maximum daily dose of 50 mg/kg TMZ for 5 consecutive days. Survival time and neurological deficit were recorded as outcome parameters. Results: In the neurotoxicity study, low dose TMZ (1 mg) was feasible to be administered into brainstem over 7 days without neurological deficit. Using high dose TMZ (5-10 mg), marked neurotoxic effect was observed. In the brainstem tumor study, survival was significantly prolonged in low dose i.c.-TMZ group compared to control rats (median survival 23.5 versus 29.5 days; p<0.01). Systemic therapy with maximal oral-TMZ dose resulted in longer survival time compared to low dose i.c.-TMZ group (median survival 33.5 versus 29.5 days; p<0.01). Conclusions: i.c.-TMZ is feasible and effective against rat brainstem glioblastoma allograft. However, we could not show superior potential of i.c.-TMZ compared to oral-TMZ administration. Modification of TMZ infusion with systemic therapy warrants future investigations.

Original languageEnglish (US)
Pages (from-to)707-713
Number of pages7
JournalChild's Nervous System
Volume28
Issue number5
DOIs
StatePublished - May 1 2012

Keywords

  • Animal model
  • Brainstem
  • Convection-enhanced delivery
  • Glioma
  • Pontine glioma
  • Temozolomide

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Fingerprint Dive into the research topics of 'The effects of temozolomide delivered by prolonged intracerebral microinfusion against the rat brainstem GBM allograft model'. Together they form a unique fingerprint.

  • Cite this