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Interstitial Infusion of Carmustine in
the Rat Brain Stem with Systemic Administration of O6-benzylguanine
Mark M. Souweidane, Giuseppe Occhiogrosso, Erika B.
Mark, Mark A. Edgar, Ira J. Dunkel
Department of Neurological Surgery
[M.M.S., G.O., E.B.M.], Department of Surgical Pathology [M.E.A.], The Weill
Medical College of Cornell University; Memorial Sloan- Kettering Cancer Center [M.M.S., G.O.,
E.B.M.]; Department of Pediatrics [I.J.D.], Memorial
Sloan-Kettering Cancer Center, New York, USA.
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.
Keywords: BCNU,
brain stem glioma, carmustine, interstitial infusion, pontine glioma
Copyright
©
2004 Kluwer Academic Publishers.
All rights reserved
Source:
doi:10.1023/B:NEON.0000024242.59770.7a
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