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

Overview

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 microl) 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 microm) 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.