Interstitial infusion of carmustine in the rat brain stem with systemic administration of O6-benzylguanine Journal Article

  


Authors: Souweidane, M. M.; Occhiogrosso, G.; Mark, E. B.; Edgar, M. A.; Dunkel, I. J.
Article Title: Interstitial infusion of carmustine in the rat brain stem with systemic administration of O6-benzylguanine
Abstract: Interstitial infusion of carmustine (BCNU) into the rat brain stem in conjunction with systemic administration of O6-benzylguanine (O6-BG) was performed in an effort to assess clinical tolerance. A total of 12 rats underwent stereotactic cannula placement into the pontine segment of the brain stem. Six of the rats underwent a 24-h infusion of BCNU (Volume of infusion [Vi] 200 μl) at its maximal concentrated dose (3.3 mg/ml) in 5% dextrose water. Six additional rats underwent 24-h infusion of BCNU preceded by an intraperitoneal injection of O6-BG at a dose of 50 mg/kg. Serial neurological examinations were performed on all animals. Histologic analyses were performed immediately or 2 weeks following sacrifice. Postoperatively, there were no neurological changes in any of the animals. Postmortem histological examination of the brains showed small pontine cavitary lesions (ranging from 20 to 250 μm) containing variable numbers of macrophages or neutrophils consistent with an inflammatory response. No changes beyond these findings indicated any histological evidence of injury. These finding were limited only to the cannula site and no changes beyond region of the cannula tract were found. These findings indicate that interstitial infusion of BCNU into the brain stem in conjunction with systemic administration of O6-BG is safe in a small animal and may serve as a potential investigative strategy for children with diffuse pontine gliomas. © 2004 Kluwer Academic Publishers.
Keywords: controlled study; drug tolerability; histopathology; postoperative period; dose response; drug safety; nonhuman; systemic therapy; comparative study; glioma; antineoplastic agent; animal cell; animal; metabolism; animals; animal tissue; antineoplastic combined chemotherapy protocols; animal experiment; animal model; brain injury; drug effect; pathology; carmustine; immune response; neutrophil; guanine; blood analysis; rat; drug derivative; drug infusion; toxicity testing; cell count; neutrophils; glucose; rats; rats, sprague-dawley; autopsy; macrophage; macrophages; pons angle tumor; brain stem; sprague dawley rat; concentration response; interstitial infusion; neurologic examination; drug indication; stereotaxic surgery; 6 o benzylguanine; brain stem glioma; dose time effect relation; infusion pump; stereotaxic techniques; pons; cannulation; intraperitoneal drug administration; injections, intraperitoneal; pontine glioma; bcnu; infusion pumps; male; article; interstitium; o(6) benzylguanine; o(6)-benzylguanine
Journal Title: Journal of Neuro-Oncology
Volume: 67
Issue: 3
ISSN: 0167-594X
Publisher: Springer  
Date Published: 2004-05-01
Start Page: 319
End Page: 326
Language: English
DOI: 10.1023/B:NEON.0000024242.59770.7a
PROVIDER: scopus
PUBMED: 15164987
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-2942735187&partnerID=40&md5=39490c73ab1bcaea0e9a07c01ae83c45
Notes: J. Neuro-Oncol. -- Cited By (since 1996):11 -- Export Date: 16 June 2014 -- CODEN: JNODD -- Source: Scopus
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MSK Authors
  1. Ira J Dunkel
    371 Dunkel
  2. Mark Musa Souweidane
    219 Souweidane
  3. Gina Ortega
    2 Ortega
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